Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Thermal immuno-nanomedicine in cancer

Nature Reviews Clinical Oncology volume 20, pages 116–134 (2023)Cite this article

Subjects

Abstract

Immunotherapy has revolutionized the treatment of patients with cancer. However, promoting antitumour immunity in patients with tumours that are resistant to these therapies remains a challenge. Thermal therapies provide a promising immune-adjuvant strategy for use with immunotherapy, mostly owing to the capacity to reprogramme the tumour microenvironment through induction of immunogenic cell death, which also promotes the recruitment of endogenous immune cells. Thus, thermal immunotherapeutic strategies for various cancers are an area of considerable research interest. In this Review, we describe the role of the various thermal therapies and provide an update on attempts to combine these with immunotherapies in clinical trials. We also provide an overview of the preclinical development of various thermal immuno-nanomedicines, which are capable of combining thermal therapies with various immunotherapy strategies in a single therapeutic platform. Finally, we discuss the challenges associated with the clinical translation of thermal immuno-nanomedicines and emphasize the importance of multidisciplinary and inter-professional collaboration to facilitate the optimal translation of this technology from bench to bedside.

Key points

  • Immunotherapy has revolutionized cancer therapy, and the clinical effectiveness of approaches such as immune-checkpoint inhibitors and cellular immunotherapies has created substantial improvements in outcomes.

  • Thermal therapies designed to deliver local hyperthermia can promote antitumour immunity via the induction of immunogenic cell death following tumour ablation and by reprogramming the tumour microenvironment.

  • Several early-phase trials combining thermal therapies with immunotherapy are either ongoing or completed, and some have provided encouraging results that support the further clinical development of combined thermal therapy–immunotherapy approaches.

  • Thermal immuno-nanomedicines are thermal therapies that also incorporate immunotherapies within a single nanoparticle, potentially enabling simultaneous activity and synergy between these two modalities.

  • Preclinical evidence suggests that thermal immuno-nanomedicines provide a promising cancer therapeutic strategy; however, coordinated efforts from multidisciplinary teams of experts will be required to drive the clinical translation of this technology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Effects of hyperthermia on innate and adaptive immunity.
Fig. 2: Graphical representation of the main thermal therapy modalities.
Fig. 3: Thermal immuno-nanomedicines.
Fig. 4: Future development of thermal immuno-nanomedicines driven by a multidisciplinary team.

Similar content being viewed by others

References

  1. Nam, J. et al. Cancer nanomedicine for combination cancer immunotherapy. Nat. Rev. Mater. 4, 398–414 (2019).

    Article  Google Scholar 

  2. Pearlman, A. H. et al. Targeting public neoantigens for cancer immunotherapy. Nat. Cancer 2, 487–497 (2021).

    Article  CAS  Google Scholar 

  3. Li, Y. et al. Targeting IL-21 to tumor-reactive T cells enhances memory T cell responses and anti-PD-1 antibody therapy. Nat. Commun. 12, 951 (2021).

    Article  CAS  Google Scholar 

  4. Sahin, U. et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature 585, 107–112 (2020).

    Article  CAS  Google Scholar 

  5. Waldman, A. D., Fritz, J. M. & Lenardo, M. J. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunol. 20, 651–668 (2020).

    Article  CAS  Google Scholar 

  6. Singh, A. K. & McGuirk, J. P. CAR T cells: continuation in a revolution of immunotherapy. Lancet Oncol. 21, E168–E178 (2020).

    Article  CAS  Google Scholar 

  7. Vitale, I., Shema, E., Loi, S. & Galluzzi, L. Intratumoral heterogeneity in cancer progression and response to immunotherapy. Nat. Med. 27, 212–224 (2021).

    Article  CAS  Google Scholar 

  8. Newman, J. H. et al. Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer. Proc. Natl Acad. Sci. USA 117, 1119–1128 (2020).

    Article  CAS  Google Scholar 

  9. Jackson, C. M., Choi, J. & Lim, M. Mechanisms of immunotherapy resistance: lessons from glioblastoma. Nat. Immunol. 20, 1100–1109 (2019).

    Article  CAS  Google Scholar 

  10. Bonaventura, P. et al. Cold tumors: a therapeutic challenge for immunotherapy. Front. Immunol. 10, 168 (2019).

    Article  CAS  Google Scholar 

  11. Certo, M., Tsai, C. H., Pucino, V., Ho, P. C. & Mauro, C. Lactate modulation of immune responses in inflammatory versus tumour microenvironments. Nat. Rev. Immunol. 21, 151–161 (2021).

    Article  CAS  Google Scholar 

  12. Chen, Y., McAndrews, K. M. & Kalluri, R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat. Rev. Clin. Oncol. 18, 792–804 (2021).

    Article  CAS  Google Scholar 

  13. Rodriguez Garcia, A. et al. CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy. Nat. Commun. 12, 877 (2021).

    Article  CAS  Google Scholar 

  14. Schmid, P. et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 21, 44–59 (2020).

    Article  CAS  Google Scholar 

  15. Adams, S. et al. Atezolizumab plus nab-paclitaxel in the treatment of metastatic triple-negative breast cancer with 2-year survival follow-up a phase 1b clinical trial. JAMA Oncol. 5, 334–342 (2019).

    Article  Google Scholar 

  16. Esperanza Rodriguez Ruiz, M., Vitale, I., Harrington, K. J., Melero, I. & Galluzzi, L. Immunological impact of cell death signaling driven by radiation on the tumor microenvironment. Nat. Immunol. 21, 120–134 (2020).

    Article  Google Scholar 

  17. Patel, R. B. et al. Low-dose targeted radionuclide therapy renders immunologically cold tumors responsive to immune checkpoint blockade. Sci. Transl. Med. 13, eabb3631 (2021).

    Article  CAS  Google Scholar 

  18. Chang, M., Hou, Z., Wang, M., Li, C. & Lin, J. Recent advances in hyperthermia therapy-based synergistic immunotherapy. Adv. Mater. 33, 2004788 (2021).

    Article  CAS  Google Scholar 

  19. Cortes, J. et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 396, 1817–1828 (2020).

    Article  Google Scholar 

  20. Schmid, P. et al. Pembrolizumab for early triple-negative breast cancer. N. Engl. J. Med. 382, 810–821 (2020).

    Article  CAS  Google Scholar 

  21. Liu, W. et al. Combination of immune checkpoint inhibitors with chemotherapy in lung cancer. OncoTargets Ther. 13, 7229–7241 (2020).

    Article  CAS  Google Scholar 

  22. Larroquette, M. et al. Combining immune checkpoint inhibitors with chemotherapy in advanced solid tumours: a review. Eur. J. Cancer 158, 47–62 (2021).

    Article  CAS  Google Scholar 

  23. Zhou, J. L., Huang, Q., Huang, Z. J. & Li, J. Q. Combining immunotherapy and radiotherapy in lung cancer: a promising future? J. Thorac. Dis. 12, 4498–4503 (2020).

    Article  Google Scholar 

  24. Shirvalilou, S. et al. Magnetic hyperthermia as an adjuvant cancer therapy in combination with radiotherapy versus radiotherapy alone for recurrent/progressive glioblastoma: a systematic review. J. Neurooncol. 152, 419–428 (2021).

    Article  Google Scholar 

  25. Li, Q. et al. Pre- and post-irradiation mild hyperthermia enabled by NIR-II for sensitizing radiotherapy. Biomaterials 257, 120235 (2020).

    Article  CAS  Google Scholar 

  26. Sen, A. et al. Mild elevation of body temperature reduces tumor interstitial fluid pressure and hypoxia and enhances efficacy of radiotherapy in murine tumor models. Cancer Res. 71, 3872–3880 (2011).

    Article  CAS  Google Scholar 

  27. Mu, C. et al. Chemotherapy sensitizes therapy-resistant cells to mild hyperthermia by suppressing heat shock protein 27 expression in triple-negative breast cancer. Clin. Cancer Res. 24, 4900–4912 (2018).

    Article  CAS  Google Scholar 

  28. Klaver, C. E. L. et al. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial. Lancet Gastroenterol. 4, 761–770 (2019).

    Google Scholar 

  29. Shin, D. H., Melnick, K. F., Tran, D. D. & Ghiaseddin, A. P. In situ vaccination with laser interstitial thermal therapy augments immunotherapy in malignant gliomas. J. Neurooncol. 151, 85–92 (2021).

    Article  Google Scholar 

  30. Napoli, A. et al. Noninvasive therapy for osteoid osteoma: a prospective developmental study with MR imaging-guided high-intensity focused ultrasound. Radiology 285, 186–196 (2017).

    Article  Google Scholar 

  31. Friedman, M. et al. Radiofrequency ablation of cancer. Cardiovasc. Interv. Radiol. 27, 427–434 (2004).

    Article  Google Scholar 

  32. Jiang, Y., Huang, J., Xu, C. & Pu, K. Activatable polymer nanoagonist for second near-infrared photothermal immunotherapy of cancer. Nat. Commun. 12, 742 (2021).

    Article  CAS  Google Scholar 

  33. Fite, B. Z. et al. Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer. Sci. Rep. 11, 927 (2021).

    Article  CAS  Google Scholar 

  34. Pan, J. et al. Combined magnetic hyperthermia and Immune therapy for primary and metastatic tumor treatments. ACS Nano 14, 1033–1044 (2020).

    Article  CAS  Google Scholar 

  35. Lerner, E. C., Edwards, R. M., Wilkinson, D. S. & Fecci, P. E. Laser ablation: heating up the anti-tumor response in the intracranial compartment. Adv. Drug Deliv. Rev. 185, 114311 (2022).

    Article  CAS  Google Scholar 

  36. Pan, Y., Liu, L., Rao, L. & Chen, X. Nanomaterial-mediated ablation therapy for cancer stem cells. Matter 5, 1367–1390 (2022).

    Article  CAS  Google Scholar 

  37. Pan, J., Xu, Y., Wu, Q., Hu, P. & Shi, J. Mild magnetic hyperthermia-activated innate immunity for liver cancer therapy. J. Am. Chem. Soc. 143, 8116–8128 (2021).

    Article  CAS  Google Scholar 

  38. Chen, Q. et al. Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism. Nat. Immunol. 7, 1299–1308 (2006).

    Article  CAS  Google Scholar 

  39. Shi, L. et al. Thermal ablation plus toripalimab in patients with advanced hepatocellular carcinoma: phase I results from a multicenter, open-label, controlled phase I/II trial (IR11330). Ann. Oncol. 32, S826–S826 (2021).

    Article  Google Scholar 

  40. Lyu, N. et al. Ablation reboots the response in advanced hepatocellular carcinoma with stable or atypical response during PD-1 therapy: a proof-of-concept study. Front. Oncol. 10, 580241 (2020).

    Article  Google Scholar 

  41. Duffy, A. G. et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J. Hepatol. 66, 545–551 (2017).

    Article  CAS  Google Scholar 

  42. Xie, C. et al. Tremelimumab in combination with microwave ablation in patients with refractory biliary tract cancer. Hepatology 69, 2048–2060 (2019).

    Article  CAS  Google Scholar 

  43. Zuo, S. et al. Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what? Theranostics 11, 7471–7487 (2021).

    Article  CAS  Google Scholar 

  44. Bailey, S. R. & Maus, M. V. Gene editing for immune cell therapies. Nat. Biotechnol. 37, 1425–1434 (2019).

    Article  CAS  Google Scholar 

  45. Fierro, J. et al. Dual-sgRNA CRISPR/Cas9 knockout of PD-L1 in human U87 glioblastoma tumor cells inhibits proliferation, invasion, and tumor-associated macrophage polarization. Sci. Rep. 12, 2417 (2022).

    Article  Google Scholar 

  46. Shi, L. et al. CRISPR knock out CTLA-4 enhances the anti-tumor activity of cytotoxic T lymphocytes. Gene 636, 36–41 (2017).

    Article  CAS  Google Scholar 

  47. Chen, Q. et al. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat. Commun. 7, 13193 (2016).

    Article  CAS  Google Scholar 

  48. Huang, L. et al. Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy. Nat. Commun. 10, 4871 (2019).

    Article  Google Scholar 

  49. Saccomandi, P., Lapergola, A., Longo, F., Schena, E. & Quero, G. Thermal ablation of pancreatic cancer: a systematic literature review of clinical practice and pre-clinical studies. Int. J. Hyperth. 35, 398–418 (2019).

    Article  Google Scholar 

  50. Chu, K. F. & Dupuy, D. E. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat. Rev. Cancer 14, 199–208 (2014).

    Article  CAS  Google Scholar 

  51. van Solinge, T. S., Nieland, L., Chiocca, E. A. & Broekman, M. L. D. Advances in local therapy for glioblastoma — taking the fight to the tumour. Nat. Rev. Neurol. 18, 221–236 (2022).

    Article  Google Scholar 

  52. Elming, P. B. et al. Hyperthermia: the optimal treatment to overcome radiation resistant hypoxia. Cancers 11, 60 (2019).

    Article  CAS  Google Scholar 

  53. Issels, R. D. et al. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma. JAMA Oncol. 4, 483–492 (2018).

    Article  Google Scholar 

  54. Krawczyk, P. M. et al. Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition. Proc. Natl Acad. Sci. USA 108, 9851–9856 (2011).

    Article  CAS  Google Scholar 

  55. Bailey, C. W. & Sydnor, M. K. Current state of tumor ablation therapies. Dig. Dis. Sci. 64, 951–958 (2019).

    Article  Google Scholar 

  56. Belyanchikov, M. A. et al. Dielectric ordering of water molecules arranged in a dipolar lattice. Nat. Commun. 11, 3927 (2020).

    Article  CAS  Google Scholar 

  57. Kok, H. P. et al. Heating technology for malignant tumors: a review. Int. J. Hyperth. 37, 711–741 (2020).

    Article  CAS  Google Scholar 

  58. Gao, D. et al. NIR/MRI-guided oxygen-independent carrier-free anti-tumor nano-theranostics. Small 18, 2106000 (2021).

    Article  Google Scholar 

  59. Gao, D. et al. Multifunctional phototheranostic nanomedicine for cancer imaging and treatment. Mater. Today Bio 5, 100035 (2020).

    Article  CAS  Google Scholar 

  60. Gao, D. et al. Targeting hypoxic tumors with hybrid nanobullets for oxygen-independent synergistic photothermal and thermodynamic therapy. Nanomicro. Lett. 13, 99 (2021).

    CAS  Google Scholar 

  61. Hammill, C. W. et al. Evaluation of a minimally invasive image-guided surgery system for hepatic ablation procedures. Surg. Innov. 21, 419–426 (2014).

    Article  Google Scholar 

  62. Patel, P., Patel, N. V. & Danish, S. F. Intracranial MR-guided laser-induced thermal therapy: single-center experience with the Visualase thermal therapy system. J. Neurosurg. 125, 853–860 (2016).

    Article  Google Scholar 

  63. Mohammadi, A. M. & Schroeder, J. L. Laser interstitial thermal therapy in treatment of brain tumors — the NeuroBlate system. Expert Rev. Med. Devices 11, 109–119 (2014).

    Article  CAS  Google Scholar 

  64. Sloan, A. E. et al. Results of the neuroblate system first-in-humans phase I clinical trial for recurrent glioblastoma. J. Neurosurg. 118, 1202–1219 (2013).

    Article  Google Scholar 

  65. Li, X. S., Lovell, J. F., Yoon, J. & Chen, X. Y. Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat. Rev. Clin. Oncol. 17, 657–674 (2020).

    Article  Google Scholar 

  66. Xia, Y. et al. Long-term effects of repeat hepatectomy vs percutaneous radiofrequency ablation among patients with recurrent hepatocellular carcinoma. JAMA Oncol. 6, 255–263 (2020).

    Article  Google Scholar 

  67. Kinoshita, T. RFA experiences, indications and clinical outcomes. Int. J. Clin. Oncol. 24, 603–607 (2019).

    Article  Google Scholar 

  68. Al Zubaidi, M., Lotter, K., Marshall, M. & Lozinskiy, M. Radiofrequency ablation for renal tumours: a retrospective study from a tertiary centre. Asian J. Urol. 9, 2214–3882 (2021).

    Google Scholar 

  69. Wan, J. & Wang, J. Current progression of radiofrequency ablation (RFA) in clinical application of lung cancer therapy. J. Biomater. Tissue Eng. 9, 417–426 (2019).

    Article  Google Scholar 

  70. Vietti Violi, N. et al. Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: a randomised controlled phase 2 trial. Lancet Gastroenterol. Hepatol. 3, 317–325 (2018).

    Article  Google Scholar 

  71. Schirmang, T. C. & Dupuy, D. E. Image-guided thermal ablation of nonresectable hepatic tumors using the Cool-Tip radiofrequency ablation system. Expert Rev. Med. Devices 4, 803–814 (2007).

    Article  Google Scholar 

  72. Gaffke, G. et al. Use of semiflexible applicators for radiofrequency ablation of liver tumors. Cardiovasc. Interv. Radiol. 29, 270–275 (2006).

    Article  CAS  Google Scholar 

  73. Solmi, L., Nigro, G. & Roda, E. Therapeutic effectiveness of echo-guided percutaneous radiofrequency ablation therapy with a LeVeen needle electrode in hepatocellular carcinoma. World J. Gastroenterol. 12, 1098–1104 (2006).

    Article  Google Scholar 

  74. Mohkam, K. et al. No-touch multibipolar radiofrequency ablation vs. surgical resection for solitary hepatocellular carcinoma ranging from 2 to 5 cm. J. Hepatol. 68, 1172–1180 (2018).

    Article  Google Scholar 

  75. King, J. et al. Percutaneous radiofrequency ablation of pulmonary metastases in patients with colorectal cancer. Br. J. Surg. 91, 217–223 (2004).

    Article  CAS  Google Scholar 

  76. Sommer, C. M. et al. CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma: Specific technical aspects and clinical results. Cardiovasc. Interv. Radiol. 36, 731–737 (2013).

    Article  CAS  Google Scholar 

  77. Wells, C. D., Kim, H. J., Moirano, M. M., Fleischer, D. E. & Sharma, V. K. Successful ablation of Barrett esophagus (BE) with dysplasia using the Halo360 ablation system: a single-center experience. Am. J. Gastroenterol. 101, S535–S535 (2006).

    Article  Google Scholar 

  78. Rothstein, R. I., Chang, K. J., Overholt, B. F., Bergman, J. J. & Shaheen, N. J. Focal ablation for treatment of dysplastic and non-dysplastic barrett esophagus: safety profile and initial experience with the Halo90 device in 508 cases. Gastrointest. Endosc. 65, AB147–AB147 (2007).

    Article  Google Scholar 

  79. Shen, R. et al. Ultrasonography-guided radiofrequency ablation combined with lauromacrogol sclerotherapy for mixed thyroid nodules. Am. J. Transl. Res. 13, 5035–5042 (2021).

    CAS  Google Scholar 

  80. Mayer, T. et al. Spinal metastases treated with bipolar radiofrequency ablation with increased (>70°C) target temperature: pain management and local tumor control. Diagn. Interv. Imaging 102, 27–34 (2021).

    Article  CAS  Google Scholar 

  81. Lorenc, T., Kocon, H. & Golebiowski, M. Computed tomography-guided percutaneous radiofrequency and laser ablation for the treatment of osteoid osteoma — long-term follow-up from 5 to 10 years. Pol. J. Radiol. 86, E19–E30 (2021).

    Article  Google Scholar 

  82. Osaki, Y. et al. Clinical effectiveness of bipolar radiofrequency ablation for small liver cancers. J. Gastroenterol. 48, 874–883 (2013).

    Article  Google Scholar 

  83. Llovet, J. M. et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat. Rev. Gastroenterol. Hepatol. 18, 293–313 (2021).

    Article  CAS  Google Scholar 

  84. Yu, M. et al. Microwave ablation of primary breast cancer inhibits metastatic progression in model mice via activation of natural killer cells. Cell. Mol. Immunol. 18, 2153–2164 (2021).

    Article  CAS  Google Scholar 

  85. Vogl, T. J. et al. A comparison between 915 MHz and 2450 MHz microwave ablation systems for the treatment of small diameter lung metastases. Diagn. Interv. Radiol. 24, 31–37 (2018).

    Article  Google Scholar 

  86. Livraghi, T., Meloni, F., Solbiati, L. & Zanus, G. Complications of microwave ablation for liver tumors: results of a multicenter study. Cardiovasc. Interv. Radiol. 35, 868–874 (2012).

    Article  Google Scholar 

  87. Imajo, K. et al. New microwave ablation system for unresectable liver tumors that forms large, spherical ablation zones. J. Gastroenterol. Hepatol. 33, 2007–2014 (2018).

    Article  Google Scholar 

  88. Alexander, E. S. et al. Microwave ablation of focal hepatic malignancies regardless of size: a 9-year retrospective study of 64 patients. Eur. J. Radiol. 84, 1083–1090 (2015).

    Article  Google Scholar 

  89. Habert, P. et al. Percutaneous lung and liver CT-guided ablation on swine model using microwave ablation to determine ablation size for clinical practice. Int. J. Hyperth. 38, 1140–1148 (2021).

    Article  CAS  Google Scholar 

  90. Medhat, E. et al. Value of microwave ablation in treatment of large lesions of hepatocellular carcinoma. J. Dig. Dis. 16, 456–463 (2015).

    Article  Google Scholar 

  91. Filippiadis, D. K. et al. Computed tomography-guided percutaneous microwave ablation of hepatocellular carcinoma in challenging locations: safety and efficacy of high-power microwave platforms. Int. J. Hyperth. 34, 863–869 (2018).

    Article  Google Scholar 

  92. Zhao, H. & Steinke, K. Long-term outcome following microwave ablation of early-stage non-small cell lung cancer. J. Med. Imaging Radiat. Oncol. 64, 787–793 (2020).

    Article  Google Scholar 

  93. Pusceddu, C., Sotgia, B., Fele, R. M. & Melis, L. Treatment of bone metastases with microwave thermal ablation. J. Vasc. Interv. Radiol. 24, 229–233 (2013).

    Article  Google Scholar 

  94. Rostas, J. W., Hong, Y. K., Schulz, B., Sanders, M. E. & Martin, R. C. G. A multi-visceral study comparing three proprietary microwave ablation devices. HPB 19, S158–S159 (2017).

    Article  Google Scholar 

  95. Peek, M. C. L. et al. Minimally invasive ablative techniques in the treatment of breast cancer: a systematic review and meta-analysis. Int. J. Hyperth. 33, 191–202 (2017).

    Article  CAS  Google Scholar 

  96. Lindner, U. et al. Focal magnetic resonance guided focused ultrasound for prostate cancer: initial North American experience. Can. Urol. Assoc. J. 6, E283–E286 (2012).

    Article  Google Scholar 

  97. Francica, G. Needle track seeding after radiofrequency ablation for hepatocellular carcinoma: prevalence, impact, and management challenge. J. Hepatocell. Carcinoma 4, 23–27 (2017).

    Article  Google Scholar 

  98. Kennedy, J. E. High-intensity focused ultrasound in the treatment of solid tumours. Nat. Rev. Cancer 5, 321–327 (2005).

    Article  CAS  Google Scholar 

  99. Rebillard, X. et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer. J. Endourol. 19, 693–701 (2005).

    Article  Google Scholar 

  100. Aliaev, I. et al. Treatment of prostatic cancer with high intensity focused ultrasound (HIFU) using Ablatherm device. Urologiia 6, 39–44 (2007).

    Google Scholar 

  101. Burtnyk, M., Hill, T., Cadieux Pitre, H. & Welch, I. Magnetic resonance image guided transurethral ultrasound prostate ablation: a preclinical safety and feasibility study with 28-day followup. J. Urol. 193, 1669–1675 (2015).

    Article  Google Scholar 

  102. Meng, Y., Hynynen, K. & Lipsman, N. Applications of focused ultrasound in the brain: from thermoablation to drug delivery. Nat. Rev. Neurol. 17, 7–22 (2021).

    Article  Google Scholar 

  103. Temple, M. J. et al. Establishing a clinical service for the treatment of osteoid osteoma using magnetic resonance-guided focused ultrasound: overview and guidelines. J. Ther. Ultrasound 4, 16–16 (2016).

    Article  Google Scholar 

  104. Dobrotwir, A. & Pun, E. Clinical 24 month experience of the first MRgFUS Unit for treatment of uterine fibroids in Australia. J. Med. Imaging Radiat. Oncol. 56, 409–416 (2012).

    Article  Google Scholar 

  105. Knuttel, F. M. et al. Early health technology assessment of magnetic resonance-guided high intensity focused ultrasound ablation for the treatment of early-stage breast cancer. J. Ther. Ultrasound 5, 1–10 (2017).

    Article  Google Scholar 

  106. Najafi, A., Fuchs, B. & Binkert, C. A. Mid-term results of MR-guided high-intensity focused ultrasound treatment for relapsing superficial desmoids. Int. J. Hyperth. 36, 537–541 (2019).

    Article  Google Scholar 

  107. Jung, S. E., Cho, S. H., Jang, J. H. & Han, J. Y. High-intensity focused ultrasound ablation in hepatic and pancreatic cancer: complications. Abdom. Imaging 36, 185–195 (2011).

    Article  Google Scholar 

  108. Zhao, J. et al. The efficacy of a new high intensity focused ultrasound therapy for locally advanced pancreatic cancer. J. Cancer Res. Clin. Oncol. 143, 2105–2111 (2017).

    Article  Google Scholar 

  109. Leslie, T. A. et al. High intensity focused ultrasound in the treatment of small kidney tumours — the Oxford experience. J. Clin. Oncol. 24, 14645–14645 (2006).

    Article  Google Scholar 

  110. Arcot, R. & Polascik, T. J. Does MRI-guided TULSA provide a targeted approach to ablation? Nat. Rev. Urol. 18, 5–6 (2021).

    Article  Google Scholar 

  111. Nair, S. M. et al. Magnetic resonance imaging-guided transurethral ultrasound ablation in patients with localised prostate cancer: 3-year outcomes of a prospective phase I study. BJU Int. 127, 544–552 (2021).

    Article  CAS  Google Scholar 

  112. Muto, S. et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn. J. Clin. Oncol. 38, 192–199 (2008).

    Article  Google Scholar 

  113. Gilchrist, R. K. et al. Selective inductive heating of lymph nodes. Ann. Surg. 146, 596–606 (1957).

    Article  CAS  Google Scholar 

  114. Gavilan, H. et al. Magnetic nanoparticles and clusters for magnetic hyperthermia: optimizing their heat performance and developing combinatorial therapies to tackle cancer. Chem. Soc. Rev. 50, 11614–11667 (2021).

    Article  CAS  Google Scholar 

  115. Song, G. et al. Carbon-coated FeCo nanoparticles as sensitive magnetic-particle-imaging tracers with photothermal and magnetothermal properties. Nat. Biomed. Eng. 4, 325–334 (2020).

    Article  CAS  Google Scholar 

  116. Liu, X. et al. Comprehensive understanding of magnetic hyperthermia for improving antitumor therapeutic efficacy. Theranostics 10, 3793–3815 (2020).

    Article  CAS  Google Scholar 

  117. Lu, C. et al. Engineering of magnetic nanoparticles as magnetic particle imaging tracers. Chem. Soc. Rev. 50, 8102–8146 (2021).

    Article  CAS  Google Scholar 

  118. Ho, D., Sun, X. & Sun, S. Monodisperse magnetic nanoparticles for theranostic applications. Acc. Chem. Res. 44, 875–882 (2011).

    Article  CAS  Google Scholar 

  119. Maier-Hauff, K. et al. Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J. Neurooncol. 103, 317–324 (2011).

    Article  Google Scholar 

  120. Galluzzi, L., Buque, A., Kepp, O., Zitvogel, L. & Kroemer, G. Immunogenic cell death in cancer and infectious disease. Nat. Rev. Immunol. 17, 97–111 (2017).

    Article  CAS  Google Scholar 

  121. Garg, A. D. & Agostinis, P. Cell death and immunity in cancer: from danger signals to mimicry of pathogen defense responses. Immunol. Rev. 280, 126–148 (2017).

    Article  CAS  Google Scholar 

  122. Li, Z., Deng, J., Sun, J. & Ma, Y. Hyperthermia targeting the tumor microenvironment facilitates immune checkpoint inhibitors. Front. Immunol. 11, 595207 (2020).

    Article  CAS  Google Scholar 

  123. Krysko, D. V. et al. Immunogenic cell death and DAMPs in cancer therapy. Nat. Rev. Cancer 12, 860–875 (2012).

    Article  CAS  Google Scholar 

  124. Munoz, N. M. et al. Immune modulation by molecularly targeted photothermal ablation in a mouse model of advanced hepatocellular carcinoma and cirrhosis. Sci. Rep. 12, 14449 (2022).

    Article  CAS  Google Scholar 

  125. Guo, D. F. et al. Exosomes from heat-stressed tumour cells inhibit tumour growth by converting regulatory T cells to Th17 cells via IL-6. Immunology 154, 132–143 (2018).

    Article  CAS  Google Scholar 

  126. Mace, T. A., Zhong, L. W., Kokolus, K. M. & Repasky, E. A. Effector CD8+ T cell IFN-γ production and cytotoxicity are enhanced by mild hyperthermia. Int. J. Hyperth. 28, 9–18 (2012).

    Article  CAS  Google Scholar 

  127. Chen, T., Guo, J., Han, C., Yang, M. & Cao, X. Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via TLR4 pathway. J. Immunol. 182, 1449–1459 (2009).

    Article  CAS  Google Scholar 

  128. Zhao, W. et al. Hyperthermia differentially regulates TLR4 and TLR2-mediated innate immune response. Immunol. Lett. 108, 137–142 (2007).

    Article  CAS  Google Scholar 

  129. Gallucci, S., Lolkema, M. & Matzinger, P. Natural adjuvants: endogenous activators of dendritic cells. Nat. Med. 5, 1249–1255 (1999).

    Article  CAS  Google Scholar 

  130. Ostberg, J. R., Dayanc, B. E., Yuan, M., Oflazoglu, E. & Repasky, E. A. Enhancement of natural killer (NK) cell cytotoxicity by fever-range thermal stress is dependent on NKG2D function and is associated with plasma membrane NKG2D clustering and increased expression of MICA on target cells. J. Leukoc. Biol. 82, 1322–1331 (2007).

    Article  CAS  Google Scholar 

  131. Bae, J.-H. et al. Quercetin enhances susceptibility to NK cell-mediated lysis of tumor cells through induction of NKG2D ligands and suppression of HSP70. J. Immunother. 33, 391–401 (2010).

    Article  CAS  Google Scholar 

  132. He, K., Liu, P. & Xu, L. X. The cryo-thermal therapy eradicated melanoma in mice by eliciting CD4+ T-cell-mediated antitumor memory immune response. Cell Death Dis. 8, e2703 (2017).

    Article  CAS  Google Scholar 

  133. Liu, Y. et al. Plasmonic gold nanostar-mediated photothermal immunotherapy for brain tumor ablation and immunologic memory. Immunother 11, 1293–1302 (2019).

    Article  CAS  Google Scholar 

  134. Hurwitz, M. D. Hyperthermia and immunotherapy: clinical opportunities. Int. J. Hyperth. 36, 4–9 (2019).

    Article  CAS  Google Scholar 

  135. Rittmeyer, A. et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389, 255–265 (2017).

    Article  Google Scholar 

  136. Wang, S. H. et al. Nanoparticle-based medicines in clinical cancer therapy. Nano Today 45, 101512 (2022).

    Article  CAS  Google Scholar 

  137. Cortes, J. et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N. Engl. J. Med. 387, 217–226 (2022).

    Article  CAS  Google Scholar 

  138. Paz Ares, L. et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N. Engl. J. Med. 379, 2040–2051 (2018).

    Article  CAS  Google Scholar 

  139. Yang, Z. et al. Fighting immune cold and reprogramming immunosuppressive tumor microenvironment with red blood cell membrane-camouflaged nanobullets. ACS Nano 14, 17442–17457 (2020).

    Article  CAS  Google Scholar 

  140. Chaudhary, N., Weissman, D. & Whitehead, K. A. mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat. Rev. Drug Discov. 20, 817–838 (2021).

    Article  CAS  Google Scholar 

  141. Saxena, M., van der Burg, S. H., Melief, C. J. M. & Bhardwaj, N. Therapeutic cancer vaccines. Nat. Rev. Cancer 21, 360–378 (2021).

    Article  CAS  Google Scholar 

  142. Teijaro, J. R. & Farber, D. L. COVID-19 vaccines: modes of immune activation and future challenges. Nat. Rev. Immunol. 21, 195–197 (2021).

    Article  CAS  Google Scholar 

  143. Li, A. W. et al. A facile approach to enhance antigen response for personalized cancer vaccination. Nat. Mater. 17, 528–534 (2018).

    Article  CAS  Google Scholar 

  144. Kuai, R., Ochyl, L. J., Bahjat, K. S., Schwendeman, A. & Moon, J. J. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat. Mater. 16, 489–496 (2017).

    Article  CAS  Google Scholar 

  145. Aikins, M. E., Xu, C. & Moon, J. J. Engineered nanoparticles for cancer vaccination and immunotherapy. Acc. Chem. Res. 53, 2094–2105 (2020).

    Article  CAS  Google Scholar 

  146. Chen, P. M. et al. Modulation of tumor microenvironment using a TLR-7/8 agonist-loaded nanoparticle system that exerts low-temperature hyperthermia and immunotherapy for in situ cancer vaccination. Biomaterials 230, 119629 (2020).

    Article  CAS  Google Scholar 

  147. Liu, L. et al. Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles. Nat. Commun. 12, 5726 (2021).

    Article  CAS  Google Scholar 

  148. Zhou, J. R., Kroll, A. V., Holay, M., Fang, R. H. & Zhang, L. F. Biomimetic nanotechnology toward personalized vaccines. Adv. Mater. 32, 1901255 (2020).

    Article  CAS  Google Scholar 

  149. Liu, W. L. et al. Cytomembrane nanovaccines show therapeutic effects by mimicking tumor cells and antigen presenting cells. Nat. Commun. 10, 3199 (2019).

    Article  Google Scholar 

  150. Chen, Q. et al. A hybrid eukaryotic-prokaryotic nanoplatform with photothermal modality for enhanced antitumor vaccination. Adv. Mater. 32, 1908185 (2020).

    Article  CAS  Google Scholar 

  151. Wang, T. et al. A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors. Nat. Commun. 9, 1532 (2018).

    Article  Google Scholar 

  152. Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).

    Article  CAS  Google Scholar 

  153. Kubli, S. P., Berger, T., Araujo, D. V., Siu, L. L. & Mak, T. W. Beyond immune checkpoint blockade: emerging immunological strategies. Nat. Rev. Drug Discov. 20, 899–919 (2021).

    Article  CAS  Google Scholar 

  154. Mellman, I., Coukos, G. & Dranoff, G. Cancer immunotherapy comes of age. Nature 480, 480–489 (2011).

    Article  CAS  Google Scholar 

  155. Lin, D. Y. W. et al. The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. Proc. Natl Acad. Sci. USA 105, 3011–3016 (2008).

    Article  CAS  Google Scholar 

  156. Leach, D. R., Krummel, M. F. & Allison, J. P. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734–1736 (1996).

    Article  CAS  Google Scholar 

  157. Pallotta, M. T. et al. Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells. Nat. Immunol. 12, 870–878 (2011).

    Article  CAS  Google Scholar 

  158. Dong, C. et al. ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 409, 97–101 (2001).

    Article  CAS  Google Scholar 

  159. Marangoni, F. et al. Expansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop. Cell 184, 3998–4015 (2021).

    Article  CAS  Google Scholar 

  160. Zaidi, N. & Jaffee, E. M. Immunotherapy transforms cancer treatment. J. Clin. Invest. 129, 46–47 (2019).

    Article  Google Scholar 

  161. Wang, Z. et al. Janus nanobullets combine photodynamic therapy and magnetic hyperthermia to potentiate synergetic anti-metastatic immunotherapy. Adv. Sci. 6, 1901690 (2019).

    Article  CAS  Google Scholar 

  162. Liu, J. et al. Tumor hypoxia-activated combinatorial nanomedicine triggers systemic antitumor immunity to effectively eradicate advanced breast cancer. Biomaterials 273, 120847 (2021).

    Article  CAS  Google Scholar 

  163. Wang, C. et al. Immunological responses triggered by photothermal therapy with carbon nanotubes in combination with anti-CTLA-4 therapy to inhibit cancer metastasis. Adv. Mater. 26, 8154–8162 (2014).

    Article  CAS  Google Scholar 

  164. Chao, Y. et al. Iron nanoparticles for low-power local magnetic hyperthermia in combination with immune checkpoint blockade for systemic antitumor therapy. Nano Lett. 19, 4287–4296 (2019).

    Article  CAS  Google Scholar 

  165. Patsoukis, N., Wang, Q., Strauss, L. & Boussiotis Vassiliki, A. Revisiting the PD-1 pathway. Sci. Adv. 6, eabd2712 (2020).

    Article  CAS  Google Scholar 

  166. Chen, L. & Han, X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J. Clin. Invest. 125, 3384–3391 (2015).

    Article  Google Scholar 

  167. Li, H., van der Merwe, P. A. & Sivakumar, S. Biomarkers of response to PD-1 pathway blockade. Br. J. Cancer 126, 1663–1675 (2022).

    Article  CAS  Google Scholar 

  168. Liu, X. et al. Ferrimagnetic vortex nanoring-mediated mild magnetic hyperthermia imparts potent immunological effect for treating cancer metastasis. ACS Nano 13, 8811–8825 (2019).

    Article  CAS  Google Scholar 

  169. Zhang, Y. et al. Native mitochondria-targeting polymeric nanoparticles for mild photothermal therapy rationally potentiated with immune checkpoints blockade to inhibit tumor recurrence and metastasis. Chem. Eng. J. 424, 130171 (2021).

    Article  CAS  Google Scholar 

  170. Duan, X., Chan, C. & Lin, W. Nanoparticle-mediated immunogenic cell death enables and potentiates cancer immunotherapy. Angew. Chem. Int. Ed. 58, 670–680 (2019).

    Article  CAS  Google Scholar 

  171. Martins, F. et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat. Rev. Clin. Oncol. 16, 563–580 (2019).

    Article  CAS  Google Scholar 

  172. McManus, M. T. & Sharp, P. A. Gene silencing in mammals by small interfering RNAs. Nat. Rev. Genet. 3, 737–747 (2002).

    Article  CAS  Google Scholar 

  173. Saha, K. et al. The NIH somatic cell genome editing program. Nature 592, 195–204 (2021).

    Article  CAS  Google Scholar 

  174. Akinc, A. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 14, 1084–1087 (2019).

    Article  CAS  Google Scholar 

  175. Saw, P. E. & Song, E. W. siRNA therapeutics: a clinical reality. Sci. China Life Sci. 63, 485–500 (2020).

    Article  CAS  Google Scholar 

  176. Liu, B. et al. Effects of gold nanoprism-assisted human PD-L1 siRNA on both gene down-regulation and photothermal therapy on lung cancer. Acta Biomater. 99, 307–319 (2019).

    Article  CAS  Google Scholar 

  177. Sánchez Rivera, F. J. & Jacks, T. Applications of the CRISPR–Cas9 system in cancer biology. Nat. Rev. Cancer 15, 387–393 (2015).

    Article  Google Scholar 

  178. Grunwald, H. A., Weitzel, A. J. & Cooper, K. L. Applications of and considerations for using CRISPR–Cas9-mediated gene conversion systems in rodents. Nat. Protoc. 17, 3–14 (2022).

    Article  CAS  Google Scholar 

  179. Strzyz, P. CRISPR–Cas9 wins nobel. Nat. Rev. Mol. Cell Biol. 21, 714–714 (2020).

    Article  CAS  Google Scholar 

  180. Wang, D., Tai, P. W. L. & Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 18, 358–378 (2019).

    Article  CAS  Google Scholar 

  181. Bulcha, J. T., Wang, Y., Ma, H., Tai, P. W. L. & Gao, G. Viral vector platforms within the gene therapy landscape. Signal Transduct. Target. Ther. 6, 53 (2021).

    Article  CAS  Google Scholar 

  182. Ou, X., Ma, Q., Yin, W., Ma, X. & He, Z. CRISPR/Cas9 gene-editing in cancer immunotherapy: promoting the present revolution in cancer therapy and exploring more. Front. Cell Dev. Biol. 9, 674467 (2021).

    Article  Google Scholar 

  183. Gillmore, J. D. et al. CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493–502 (2021).

    Article  CAS  Google Scholar 

  184. Tang, H. et al. Reprogramming the tumor microenvironment through second-near-infrared-window photothermal genome editing of PD-L1 mediated by supramolecular gold nanorods for enhanced cancer immunotherapy. Adv. Mater. 33, 2006003 (2021).

    Article  CAS  Google Scholar 

  185. Logtenberg, M. E. W., Scheeren, F. A. & Schumacher, T. N. The CD47-SIRPα immune checkpoint. Immunity 52, 742–752 (2020).

    Article  CAS  Google Scholar 

  186. Sikic, B. I. et al. First-in-human, first-in-class phase I trial of the anti-CD47 antibody Hu5F9-G4 in patients with advanced cancers. J. Clin. Oncol. 37, 946–953 (2019).

    Article  CAS  Google Scholar 

  187. Advani, R. et al. CD47 blockade by Hu5F9-G4 and Rituximab in non-hodgkin’s lymphoma. N. Engl. J. Med. 379, 1711–1721 (2018).

    Article  CAS  Google Scholar 

  188. Liu, X. et al. CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. Nat. Med. 21, 1209–1215 (2015).

    Article  CAS  Google Scholar 

  189. Zhou, F. et al. Tumor microenvironment-activatable prodrug vesicles for nanoenabled cancer chemoimmunotherapy combining immunogenic cell death induction and CD47 blockade. Adv. Mater. 31, 1805888 (2019).

    Article  Google Scholar 

  190. Cheng, L., Zhang, X., Tang, J., Lv, Q. & Liu, J. Gene-engineered exosomes-thermosensitive liposomes hybrid nanovesicles by the blockade of CD47 signal for combined photothermal therapy and cancer immunotherapy. Biomaterials 275, 120964 (2021).

    Article  CAS  Google Scholar 

  191. Chang, M. et al. Colorectal tumor microenvironment-activated bio-decomposable and metabolizable Cu2O@CaCO3 nanocomposites for synergistic oncotherapy. Adv. Mater. 32, 2004647 (2020).

    Article  CAS  Google Scholar 

  192. Zhang, X. et al. A MXene-based bionic cascaded-enzyme nanoreactor for tumor phototherapy/enzyme dynamic therapy and hypoxia-activated chemotherapy. Nanomicro Lett. 14, 22 (2021).

    Google Scholar 

  193. Puccetti, P. & Grohmann, U. IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-κB activation. Nat. Rev. Immunol. 7, 817–823 (2007).

    Article  CAS  Google Scholar 

  194. Mellor, A. L. & Munn, D. H. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 4, 762–774 (2004).

    Article  CAS  Google Scholar 

  195. Patel, C. H., Leone, R. D., Horton, M. R. & Powell, J. D. Targeting metabolism to regulate immune responses in autoimmunity and cancer. Nat. Rev. Drug Discov. 18, 669–688 (2019).

    Article  CAS  Google Scholar 

  196. Wang, Y. et al. Immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine. Bioact. Mater. 6, 1513–1527 (2021).

    Article  CAS  Google Scholar 

  197. Le Naour, J., Galluzzi, L., Zitvogel, L., Kroemer, G. & Vacchelli, E. Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology 9, 1777625 (2020).

    Article  Google Scholar 

  198. Peng, J. et al. Photosensitizer micelles together with IDO inhibitor enhance cancer photothermal therapy and immunotherapy. Adv. Sci. 5, 1700891 (2018).

    Article  Google Scholar 

  199. Guo, Y. X. et al. Indoleamine 2,3-dioxygenase (Ido) inhibitors and their nanomedicines for cancer immunotherapy. Biomaterials 276, 121018 (2021).

    Article  CAS  Google Scholar 

  200. Jiang, W. et al. Reversing immunosuppression in hypoxic and immune-cold tumors with ultrathin oxygen self-supplementing polymer nanosheets under near infrared light irradiation. Adv. Funct. Mater. 31, 2100354 (2021).

    Article  CAS  Google Scholar 

  201. Ren, X. et al. Intelligent nanomedicine approaches using medical gas-mediated multi-therapeutic modalities against cancer. J. Biomed. Nanotechnol. 18, 24–49 (2022).

    Article  CAS  Google Scholar 

  202. Kashiwagi, S. et al. Perivascular nitric oxide gradients normalize tumor vasculature. Nat. Med. 14, 255–257 (2008).

    Article  CAS  Google Scholar 

  203. Sung, Y. C. et al. Delivery of nitric oxide with a nanocarrier promotes tumour vessel normalization and potentiates anti-cancer therapies. Nat. Nanotechnol. 14, 1160–1169 (2019).

    Article  CAS  Google Scholar 

  204. Sadelain, M., Rivière, I. & Riddell, S. Therapeutic T cell engineering. Nature 545, 423–431 (2017).

    Article  CAS  Google Scholar 

  205. Perez, C. R. & De Palma, M. Engineering dendritic cell vaccines to improve cancer immunotherapy. Nat. Commun. 10, 5408 (2019).

    Article  Google Scholar 

  206. Weber, E. W., Maus, M. V. & Mackall, C. L. The emerging landscape of immune cell therapies. Cell 181, 46–62 (2020).

    Article  CAS  Google Scholar 

  207. Santos, P. M. & Butterfield, L. H. Dendritic cell–based cancer vaccines. J. Immunol. 200, 443–449 (2018).

    Article  CAS  Google Scholar 

  208. Lu, J. & Jiang, G. The journey of CAR-T therapy in hematological malignancies. Mol. Cancer 21, 194 (2022).

    Article  Google Scholar 

  209. Zhang, H., Bu, C., Peng, Z., Luo, M. & Li, C. The efficacy and safety of anti-CLL1 based CAR-T cells in children with relapsed or refractory acute myeloid leukemia: a multicenter interim analysis. J. Clin. Oncol. 39, 10000 (2021).

    Article  Google Scholar 

  210. Ying, Z. et al. Relmacabtagene autoleucel (relma-cel) CD19 CAR-T therapy for adults with heavily pretreated relapsed/refractory large B-cell lymphoma in China. Cancer Med. 10, 999–1011 (2021).

    Article  CAS  Google Scholar 

  211. Piehler, S. et al. Hyperthermia affects collagen fiber architecture and induces apoptosis in pancreatic and fibroblast tumor hetero-spheroids in vitro. Nanomedicine 28, 102183 (2020).

    Article  CAS  Google Scholar 

  212. Beola, L. et al. Dual role of magnetic nanoparticles as intracellular hotspots and extracellular matrix disruptors triggered by magnetic hyperthermia in 3D cell culture models. ACS Appl. Mater. Interfaces 10, 44301–44313 (2018).

    Article  CAS  Google Scholar 

  213. Gouarderes, S., Mingotaud, A. F., Vicendo, P. & Gibot, L. Vascular and extracellular matrix remodeling by physical approaches to improve drug delivery at the tumor site. Expert Opin. Drug Deliv. 17, 1703–1726 (2020).

    Article  CAS  Google Scholar 

  214. Chen, Q. et al. Photothermal therapy promotes tumor infiltration and antitumor activity of CAR T cells. Adv. Mater. 31, 1900192 (2019).

    Article  Google Scholar 

  215. Ye, Y. et al. A melanin-mediated cancer immunotherapy patch. Sci. Immunol. 2, eaan5692 (2017).

    Article  Google Scholar 

  216. Bear, A. S. et al. Elimination of metastatic melanoma using gold nanoshell-enabled photothermal therapy and adoptive T cell transfer. PLoS One 8, e69073 (2013).

    Article  CAS  Google Scholar 

  217. Miller, I. C. et al. Enhanced intratumoural activity of CAR T cells engineered to produce immunomodulators under photothermal control. Nat. Biomed. Eng. 5, 1348–1359 (2021).

    Article  CAS  Google Scholar 

  218. Xiong, R. et al. Photothermal nanofibres enable safe engineering of therapeutic cells. Nat. Nanotechnol. 16, 1281–1291 (2021).

    Article  CAS  Google Scholar 

  219. Dranoff, G. Cytokines in cancer pathogenesis and cancer therapy. Nat. Rev. Cancer 4, 11–22 (2004).

    Article  CAS  Google Scholar 

  220. Briukhovetska, D. et al. Interleukins in cancer: from biology to therapy. Nat. Rev. Cancer 21, 481–499 (2021).

    Article  CAS  Google Scholar 

  221. Propper, D. J. & Balkwill, F. R. Harnessing cytokines and chemokines for cancer therapy. Nat. Rev. Clin. Oncol. 19, 237–253 (2022).

    Article  CAS  Google Scholar 

  222. Hutmacher, C. & Neri, D. Antibody-cytokine fusion proteins: Biopharmaceuticals with immunomodulatory properties for cancer therapy. Adv. Drug Deliv. Rev. 141, 67–91 (2019).

    Article  CAS  Google Scholar 

  223. Huang, H., Feng, W., Chen, Y. & Shi, J. Inorganic nanoparticles in clinical trials and translations. Nano Today 35, 100972 (2020).

    Article  CAS  Google Scholar 

  224. Liu, Y. et al. Metal-based nanoenhancers for future radiotherapy: radiosensitizing and synergistic effects on tumor cells. Theranostics 8, 1824–1849 (2018).

    Article  CAS  Google Scholar 

  225. Tamarkin, L., Myer, L., Haynes, R. & Paciotti, G. CYT-6091 (Aurimune™): a colloidal gold-based tumor-targeted nanomedicine. MRS Proc. 1019, FF01–FF10 (2007).

    Google Scholar 

  226. Teo, P. et al. Complex of TNF-α and modified Fe3O4 nanoparticles suppresses tumor growth by magnetic induction hyperthermia. Cancer Biother. Radiopharm. 32, 379–386 (2017).

    CAS  Google Scholar 

  227. Lin, X. et al. Localized NIR-II photo-immunotherapy through the combination of photothermal ablation and in situ generated interleukin-12 cytokine for efficiently eliminating primary and abscopal tumors. Nanoscale 13, 1745–1758 (2021).

    Article  CAS  Google Scholar 

  228. Antonio Chiocca, E. Oncolytic viruses. Nat. Rev. Cancer 2, 938–950 (2002).

    Article  CAS  Google Scholar 

  229. Kaufman, H. L., Kohlhapp, F. J. & Zloza, A. Oncolytic viruses: a new class of immunotherapy drugs. Nat. Rev. Drug Discov. 14, 642–662 (2015).

    Article  CAS  Google Scholar 

  230. Tian, Y., Xie, D. & Yang, L. Engineering strategies to enhance oncolytic viruses in cancer immunotherapy. Signal Transduct. Target. Ther. 7, 117 (2022).

    Article  Google Scholar 

  231. Dolgin, E. Oncolytic viruses get a boost with first FDA-approval recommendation. Nat. Rev. Drug Discov. 14, 369–371 (2015).

    Article  CAS  Google Scholar 

  232. Volker, S. A new strategy of cancer immunotherapy combining hyperthermia/oncolytic virus pretreatment with specific autologous anti-tumor vaccination. Cancer Vaccines 2, 1006 (2017).

    Google Scholar 

  233. Chen, R. et al. An analytical solution for temperature distributions in hepatic radiofrequency ablation incorporating the heat-sink effect of large vessels. Phys. Med. Biol. 63, 235026 (2018).

    Article  Google Scholar 

  234. Zhang, X. M. et al. Methotrexate-loaded PLGA nanobubbles for ultrasound imaging and synergistic targeted therapy of residual tumor during HIFU ablation. Biomaterials 35, 5148–5161 (2014).

    Article  CAS  Google Scholar 

  235. VanOsdol, J. et al. Sequential HIFU heating and nanobubble encapsulation provide efficient drug penetration from stealth and temperature sensitive liposomes in colon cancer. J. Control. Rel. 247, 55–63 (2017).

    Article  CAS  Google Scholar 

  236. Sweeney, E. E., Cano Mejia, J. & Fernandes, R. Photothermal therapy generates a thermal window of immunogenic cell death in neuroblastoma. Small 14, 1800678 (2018).

    Article  Google Scholar 

  237. Nguyen, H. T., Tran, K. K., Sun, B. B. & Shen, H. Activation of inflammasomes by tumor cell death mediated by gold nanoshells. Biomaterials 33, 2197–2205 (2012).

    Article  CAS  Google Scholar 

  238. Kokuryo, D., Kumamoto, E. & Kuroda, K. Recent technological advancements in thermometry. Adv. Drug Deliv. Rev. 163, 19–39 (2020).

    Article  Google Scholar 

  239. Saccomandi, P., Schena, E. & Pacella, C. M. in Image-guided Laser Ablation (eds Pacella, C. M., Jiang, T. & Mauri, G.) 145–151 (Springer, 2020).

  240. Zhao, T. R., Desjardins, A. E., Ourselin, S., Vercauteren, T. & Xia, W. F. Minimally invasive photoacoustic imaging: current status and future perspectives. Photoacoustics 16, 100146 (2019).

    Article  Google Scholar 

  241. Goldenberg, S. L., Nir, G. & Salcudean, S. E. A new era: artificial intelligence and machine learning in prostate cancer. Nat. Rev. Urol. 16, 391–403 (2019).

    Article  Google Scholar 

  242. Acosta, J. N., Falcone, G. J., Rajpurkar, P. & Topol, E. J. Multimodal biomedical AI. Nat. Med. 28, 1773–1784 (2022).

    Article  CAS  Google Scholar 

  243. Denu, R. A. et al. Influence of patient, physician, and hospital characteristics on the receipt of guideline-concordant care for inflammatory breast cancer. Cancer Epidemiol. 40, 7–14 (2016).

    Article  Google Scholar 

  244. Zhou, J., Zeng, Z. & Li, L. A meta-analysis of watson for oncology in clinical application. Sci. Rep. 11, 5792 (2021).

    Article  Google Scholar 

  245. Sindhwani, S. et al. The entry of nanoparticles into solid tumours. Nat. Mater. 19, 566–575 (2020).

    Article  CAS  Google Scholar 

  246. de Lazaro, I. & Mooney, D. J. Obstacles and opportunities in a forward vision for cancer nanomedicine. Nat. Mater. 20, 1469–1479 (2021).

    Article  Google Scholar 

  247. Stapleton, S. et al. Radiation and heat improve the delivery and efficacy of nanotherapeutics by modulating intratumoral fluid dynamics. ACS Nano 12, 7583–7600 (2018).

    Article  CAS  Google Scholar 

  248. Theek, B. et al. Sonoporation enhances liposome accumulation and penetration in tumors with low EPR. J. Control. Rel. 231, 77–85 (2016).

    Article  CAS  Google Scholar 

  249. Golombek, S. K. et al. Tumor targeting via EPR: strategies to enhance patient responses. Adv. Drug Deliv. Rev. 130, 17–38 (2018).

    Article  CAS  Google Scholar 

  250. Chauhan, V. P. et al. Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. Nat. Nanotechnol. 7, 383–388 (2012).

    Article  CAS  Google Scholar 

  251. Tong, R. T. et al. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res. 64, 3731–3736 (2004).

    Article  CAS  Google Scholar 

  252. Nel, A., Ruoslahti, E. & Meng, H. New insights into “permeability” as in the enhanced permeability and retention effect of cancer nanotherapeutics. ACS Nano 11, 9567–9569 (2017).

    Article  CAS  Google Scholar 

  253. Autio, K. A. et al. Safety and efficacy of BIND-014, a docetaxel nanoparticle targeting prostate-specific membrane antigen for patients with metastatic castration-resistant prostate cancer a phase 2 clinical trial. JAMA Oncol. 4, 1344–1351 (2018).

    Article  Google Scholar 

  254. Wheeler, K. E. et al. Environmental dimensions of the protein corona. Nat. Nanotechnol. 16, 617–629 (2021).

    Article  CAS  Google Scholar 

  255. Witwer, K. W. & Wolfram, J. Extracellular vesicles versus synthetic nanoparticles for drug delivery. Nat. Rev. Mater. 6, 103–106 (2021).

    Article  CAS  Google Scholar 

  256. FDA. 501(k) Premarket Notification 042216 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K042216 (2022).

  257. FDA. Starburst https://fda.report/GUDID/H7877001023300 (2018).

  258. FDA. 501(k) Summary (K140495) https://www.accessdata.fda.gov/cdrh_docs/pdf14/K140495.pdf (2014).

  259. FDA. 501(k) Premarket Notification K073207 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K073207 (2022).

  260. FDA. 510(k) Premarket Notification K093855 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K093855 (2022).

  261. FDA. 510(k) Premarket Notification K093008 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K093008 (2010).

  262. FDA. Letter to Baylis Medical Company Inc re. K161949 https://www.accessdata.fda.gov/cdrh_docs/pdf16/K161949.pdf (2017).

  263. Whooley, S. FDA clears Stryker bone tumor ablation system. Mass Device https://www.massdevice.com/fda-clears-stryker-bone-tumor-ablation/ (2022).

  264. FDA. Letter to Covidien LLC re. K193232 https://www.accessdata.fda.gov/cdrh_docs/pdf19/K193232.pdf (2020).

  265. FDA. 510(k) Premarket Notification K173756 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K173756 (2018).

  266. FDA. 510(k) Premarket Notification K083157 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K083157 (2009).

  267. Microsulis wins FDA approval for upgraded microwave tissue ablation applicator. Medical Device Network https://www.medicaldevice-network.com/uncategorized/newsmicrosulis-wins-fda-approval-for-upgraded-microwave-tissue-ablation-applicator/ (2012).

  268. FDA clears Covidien Ltd evident microwave ablation system for use in nonresectable liver tumor ablation. Biospace https://www.biospace.com/article/releases/fda-clears-covidien-ltd-evident-microwave-ablation-system-for-use-in-nonresectable-liver-tumor-ablation-/ (2008).

  269. FDA. 510(k) Summary Visualase Thermal Therapy System https://www.accessdata.fda.gov/cdrh_docs/pdf8/K081656.pdf (2008).

  270. FDA. Letter to Monteris Medical re K201056 https://www.accessdata.fda.gov/cdrh_docs/pdf20/K201056.pdf (2020).

  271. FDA. 510(k) Premarket Notification K160942 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K160942 (2016).

  272. FDA. 510(k) Premarket Notification K153023 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K153023 (2015).

  273. FDA. Letter to Profound Medical Inc re. K191200 https://www.accessdata.fda.gov/cdrh_docs/pdf19/K191200.pdf (2019).

  274. FDA. Premarket Approval (PMA) P150038 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P150038S006 (2018).

  275. FDA. Recently approved devices h190003 https://www.fda.gov/medical-devices/recently-approved-devices/sonalleve-mr-hifu-h190003 (2020).

  276. Ritchie, R. W. et al. Extracorporeal high intensity focused ultrasound for renal tumours: a 3-year follow-up. BJU Int. 106, 1004–1009 (2010).

    Article  Google Scholar 

  277. Zhao, H. et al. Concurrent gemcitabine and high-intensity focused ultrasound therapy in patients with locally advanced pancreatic cancer. Anticancer Drugs 21, 447–452 (2010).

    Article  CAS  Google Scholar 

  278. Onik, G. et al. Abstract 6540: Regression of metastatic cancer and abscopal effects following in situ vaccination by cryosurgical tumor cell lysis and intratumoral immunotherapy: a case series. Cancer Res. 80, 6540–6540 (2020).

    Article  Google Scholar 

Download references

Acknowledgements

X.Z., G.Y. and M.G. acknowledge support from Harvard/MIT. Z.Y. acknowledges research support from the National Natural Science Foundation of China (51703178), China Postdoctoral Science Foundation (2019M663742), Natural Science Foundation of Shaanxi Province (2022JM183), Natural Science Foundation of Zhejiang Province (LWY20H180002), Shaanxi Provincial Key R&D Program (2022SF-342) and Fundamental Research Funds for the Central Universities (xpt012022030, xtr052022012). D.G. acknowledges research support from the National Natural Science Foundation of China (51903203), China Postdoctoral Science Foundation (2019M653661) and Fundamental Research Funds for the Central Universities (xzy012022037). L.J. acknowledges research support from The Program of Innovative Research Team (in Science and Technology) University of Henan Province (23IRTSTHN008) and the Zhongyuan Thousand Talents Plan. Z.T. acknowledges research support from the National Natural Science Foundation of China (82070751).

Author information

Author notes

  1. These authors contributed equally: Zhe Yang, Di Gao, Jing Zhao.

Authors and Affiliations

  1. The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, China

    Zhe Yang, Di Gao, Ying Wang, Xuechun Ren & Zhongmin Tian

  2. Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi’an, China

    Jing Zhao

  3. School of Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Gaojie Yang & Ming Guo

  4. Department of Chemistry, Korea University, Seoul, Republic of Korea

    Jong Seung Kim

  5. International Joint Research Laboratory for Biomedical Nanomaterials of Henan, Zhoukou Normal University, Zhoukou, China

    Lin Jin

  6. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

    Xingcai Zhang

Authors
  1. Zhe Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Di Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gaojie Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ming Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xuechun Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jong Seung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lin Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zhongmin Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xingcai Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Z.Y., D.G., J.Z., G.Y., Y.W., X.R., L.J. and X.Z. researched data for the manuscript and wrote the manuscript. All authors made a substantial contribution to discussions of content and reviewed and/or edited the manuscript prior to submission.

Corresponding authors

Correspondence to Zhe Yang, Lin Jin, Zhongmin Tian or Xingcai Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Clinical Oncology thanks H. Zhang and the other, anonymous, reviewer(s), for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, Z., Gao, D., Zhao, J. et al. Thermal immuno-nanomedicine in cancer. Nat Rev Clin Oncol 20, 116–134 (2023). https://doi.org/10.1038/s41571-022-00717-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41571-022-00717-y

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research