Skip to main content

Advertisement

SpringerLink
Log in

Seeing the forest and the tree: TILs and PD-L1 as immune biomarkers

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Here we will provide an immune-focussed overview of biomarkers in early and advanced stage breast cancer. It should be noted from the outset that all the biomarkers under discussion here have not been tested in prospective clinical trials to determine their predictive performance. Such trials require very large sample sizes due to the statistical burden of testing an interaction between a treatment and a biomarker, which is compounded by the heterogeneous biology of breast cancer (Polley et al. in J Natl Cancer Inst 105:1677–1683 2013 [1]). For a detailed discussion of the immunobiology of breast cancer, analytical aspects of these biomarkers, emerging biomarkers such as tumour mutation burden and detailed immunotherapy clinical trial data, see other articles in this issue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

Not applicable.

Code availability

Not applicable.

References

  1. Polley M-YC, Freidlin B, Korn EL et al (2013) Statistical and practical considerations for clinical evaluation of predictive biomarkers. J Natl Cancer Inst 105:1677–1683. https://doi.org/10.1093/jnci/djt282

    Article  PubMed  PubMed Central  Google Scholar 

  2. Sistrunk WE, Maccarty WC (1922) Life expectancy following radical amputation for carcinoma of the breast: a clinical and pathologic study of 218 cases. Ann Surg 75:61–69

    PubMed  PubMed Central  CAS  Google Scholar 

  3. Salgado R, Denkert C, Demaria S et al (2015) The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an international TILs working group 2014. Ann Oncol 26:259–271. https://doi.org/10.1093/annonc/mdu450

    Article  PubMed  CAS  Google Scholar 

  4. Denkert C, Wienert S, Poterie A et al (2016) Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group. Mod Pathol 29:1155–1164. https://doi.org/10.1038/modpathol.2016.109

    Article  PubMed  CAS  Google Scholar 

  5. Kos Z, Roblin E, Kim RS et al (2020) Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. NPJ Breast Cancer 6:17. https://doi.org/10.1038/s41523-020-0156-0

    Article  PubMed  PubMed Central  Google Scholar 

  6. (2021) TILs education: what they are and what they do. https://www.youtube.com/watch?v=aPa-pXIBBlU

  7. Ruffell B, Au A, Rugo HS et al (2012) Leukocyte composition of human breast cancer. Proc Natl Acad Sci USA 109:2796–2801. https://doi.org/10.1073/pnas.1104303108

    Article  PubMed  Google Scholar 

  8. Buisseret L, Garaud S, de Wind A et al (2017) Tumor-infiltrating lymphocyte composition, organization and PD-1/ PD-L1 expression are linked in breast cancer. Oncoimmunology 6:e1257452. https://doi.org/10.1080/2162402X.2016.1257452

    Article  PubMed  CAS  Google Scholar 

  9. Savas P, Virassamy B, Ye C et al (2018) Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis. Nat Med 24:986–993. https://doi.org/10.1038/s41591-018-0078-7

    Article  PubMed  CAS  Google Scholar 

  10. Azizi E, Carr AJ, Plitas G et al (2018) Single-cell map of diverse immune phenotypes in the breast tumor microenvironment. Cell 174:1293-1308.e36. https://doi.org/10.1016/j.cell.2018.05.060

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Keren L, Bosse M, Marquez D et al (2018) A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 174:1373-1387.e19. https://doi.org/10.1016/j.cell.2018.08.039

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Loi S, Drubay D, Adams S et al (2019) Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers. J Clin Oncol 37:559–569. https://doi.org/10.1200/JCO.18.01010

    Article  PubMed  PubMed Central  Google Scholar 

  13. Burstein HJ, Curigliano G, Loibl S et al (2019) Estimating the benefits of therapy for early stage breast cancer: the St Gallen international consensus guidelines for the primary therapy of early breast cancer 2019. Ann Oncol. https://doi.org/10.1093/annonc/mdz235

    Article  PubMed  PubMed Central  Google Scholar 

  14. Cardoso F, Kyriakides S, Ohno S et al (2019) Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 30:1194–1220. https://doi.org/10.1093/annonc/mdz173

    Article  PubMed  CAS  Google Scholar 

  15. WHO classification of tumours editorial board (2019) Breast tumours. International agency for research on cancer. https://publications.iarc.fr/581

  16. Park JH, Jonas SF, Bataillon G et al (2019) Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy. Ann Oncol. https://doi.org/10.1093/annonc/mdz395

    Article  PubMed  PubMed Central  Google Scholar 

  17. De Jong VMT, Wang Y, Opdam M et al (2020) 159O prognostic value of tumour infiltrating lymphocytes in young triple negative breast cancer patients who did not receive adjuvant systemic treatment; by the PARADIGM study group. Ann Oncol 31:S303. https://doi.org/10.1016/j.annonc.2020.08.281

    Article  Google Scholar 

  18. Loi S, Michiels S, Salgado R et al (2014) Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol 25:1544–1550. https://doi.org/10.1093/annonc/mdu112

    Article  PubMed  CAS  Google Scholar 

  19. Salgado R, Denkert C, Campbell C et al (2015) Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumab: a secondary analysis of the NeoALTTO trial. JAMA Oncol 1:448–454. https://doi.org/10.1001/jamaoncol.2015.0830

    Article  PubMed  PubMed Central  Google Scholar 

  20. Denkert C, von Minckwitz G, Darb-Esfahani S et al (2018) Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol 19:40–50. https://doi.org/10.1016/S1470-2045(17)30904-X

    Article  PubMed  Google Scholar 

  21. Loi S, Sirtaine N, Piette F et al (2013) Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02–98. J Clin Oncol 31:860–867. https://doi.org/10.1200/JCO.2011.41.0902

    Article  PubMed  CAS  Google Scholar 

  22. Dieci MV, Mathieu MC, Guarneri V et al (2015) Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials. Ann Oncol 26:1698–1704. https://doi.org/10.1093/annonc/mdv239

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Krishnamurti U, Wetherilt CS, Yang J et al (2017) Tumor-infiltrating lymphocytes are significantly associated with better overall survival and disease-free survival in triple-negative but not estrogen receptor-positive breast cancers. Hum Pathol 64:7–12. https://doi.org/10.1016/j.humpath.2017.01.004

    Article  PubMed  CAS  Google Scholar 

  24. Criscitiello C, Vingiani A, Maisonneuve P et al (2020) Tumor-infiltrating lymphocytes (TILs) in ER+/HER2-breast cancer. Breast Cancer Res Treat 183:347–354. https://doi.org/10.1007/s10549-020-05771-7

    Article  PubMed  CAS  Google Scholar 

  25. Desmedt C, Salgado R, Fornili M et al (2018) Immune infiltration in invasive lobular breast cancer. J Natl Cancer Inst 110:768–776. https://doi.org/10.1093/jnci/djx268

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Lundgren C, Bendahl P-O, Ekholm M et al (2020) Tumour-infiltrating lymphocytes as a prognostic and tamoxifen predictive marker in premenopausal breast cancer: data from a randomised trial with long-term follow-up. Breast Cancer Res 22:140. https://doi.org/10.1186/s13058-020-01364-w

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Denkert C, Loibl S, Noske A et al (2010) Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28:105–113. https://doi.org/10.1200/JCO.2009.23.7370

    Article  PubMed  CAS  Google Scholar 

  28. Dieci MV, Criscitiello C, Goubar A et al (2014) Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study. Ann Oncol 25:611–618. https://doi.org/10.1093/annonc/mdt556

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Luen SJ, Salgado R, Dieci MV et al (2019) Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy. Ann Oncol 30:236–242. https://doi.org/10.1093/annonc/mdy547

    Article  PubMed  CAS  Google Scholar 

  30. Luen SJ, Salgado R, Fox S et al (2017) Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study. Lancet Oncol 18:52–62. https://doi.org/10.1016/S1470-2045(16)30631-3

    Article  PubMed  CAS  Google Scholar 

  31. Szekely B, Bossuyt V, Li X et al (2018) Immunological differences between primary and metastatic breast cancer. Ann Oncol 29:2232–2239. https://doi.org/10.1093/annonc/mdy399

    Article  PubMed  CAS  Google Scholar 

  32. He T-F, Yost SE, Frankel PH et al (2020) Multi-panel immunofluorescence analysis of tumor infiltrating lymphocytes in triple negative breast cancer: Evolution of tumor immune profiles and patient prognosis. PLoS ONE 15:e0229955. https://doi.org/10.1371/journal.pone.0229955

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Hutchinson KE, Yost SE, Chang C-W et al (2020) Comprehensive profiling of poor-risk paired primary and recurrent triple-negative breast cancers reveals immune phenotype shifts. Clin Cancer Res 26:657–668

    Article  CAS  PubMed  Google Scholar 

  34. Loi S, Adams S, Schmid P et al (2017) Relationship between tumor infiltrating lymphocyte (TIL) levels and response to pembrolizumab (pembro) in metastatic triple-negative breast cancer (mTNBC): results from KEYNOTE-086. Ann Oncol 28:LBA13. https://doi.org/10.1093/annonc/mdx440.005

    Article  Google Scholar 

  35. Loi S, Giobbie-Hurder A, Gombos A et al (2019) Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b–2 trial. Lancet Oncol. https://doi.org/10.1016/S1470-2045(18)30812-X

    Article  PubMed  Google Scholar 

  36. Emens LA, Cruz C, Eder JP et al (2019) Long-term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer: a phase 1 study. JAMA Oncol 5:74–82. https://doi.org/10.1001/jamaoncol.2018.4224

    Article  PubMed  Google Scholar 

  37. Vennapusa B, Baker B, Kowanetz M et al (2019) Development of a PD-L1 complementary diagnostic immunohistochemistry assay (SP142) for atezolizumab. Appl Immunohistochem Mol Morphol 27:92–100. https://doi.org/10.1097/PAI.0000000000000594

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Sobral-Leite M, Van de Vijver K, Michaut M et al (2018) Assessment of PD-L1 expression across breast cancer molecular subtypes, in relation to mutation rate, BRCA1-like status, tumor-infiltrating immune cells and survival. Oncoimmunology 7:e1509820. https://doi.org/10.1080/2162402X.2018.1509820

    Article  PubMed  PubMed Central  Google Scholar 

  39. Liu Y, Zugazagoitia J, Ahmed FS et al (2020) Immune cell PD-L1 colocalizes with macrophages and is associated with outcome in PD-1 pathway blockade therapy. Clin Cancer Res 26:970–977. https://doi.org/10.1158/1078-0432.CCR-19-1040

    Article  PubMed  CAS  Google Scholar 

  40. Gonzalez-Ericsson PI, Stovgaard ES, Sua LF et al (2020) The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice. J Pathol 250:667–684. https://doi.org/10.1002/path.5406

    Article  PubMed  CAS  Google Scholar 

  41. Salgado R, Bellizzi AM, Rimm D et al (2020) How current assay approval policies are leading to unintended imprecision medicine. Lancet Oncol 21:1399–1401. https://doi.org/10.1016/S1470-2045(20)30592-1

    Article  PubMed  Google Scholar 

  42. Matikas A, Zerdes I, Lövrot J et al (2019) Prognostic implications of PD-L1 expression in breast cancer: systematic review and meta-analysis of immunohistochemistry and pooled analysis of transcriptomic data. Clin Cancer Res 25:5717–5726. https://doi.org/10.1158/1078-0432.CCR-19-1131

    Article  PubMed  CAS  Google Scholar 

  43. Noske A, Möbus V, Weber K et al (2019) Relevance of tumour-infiltrating lymphocytes, PD-1 and PD-L1 in patients with high-risk, nodal-metastasised breast cancer of the German adjuvant intergroup node-positive study. Eur J Cancer 114:76–88. https://doi.org/10.1016/j.ejca.2019.04.010

    Article  PubMed  Google Scholar 

  44. Emens LA, Esteva FJ, Beresford M et al (2020) Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Lancet Oncol 21:1283–1295. https://doi.org/10.1016/S1470-2045(20)30465-4

    Article  PubMed  CAS  Google Scholar 

  45. Rugo HS, Delord J-P, Im S-A et al (2018) Safety and antitumor activity of pembrolizumab in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. Clin Cancer Res 24:2804–2811. https://doi.org/10.1158/1078-0432.CCR-17-3452

    Article  PubMed  CAS  Google Scholar 

  46. Shah AN, Flaum L, Helenowski I et al (2020) Phase II study of pembrolizumab and capecitabine for triple negative and hormone receptor-positive, HER2-negative endocrine-refractory metastatic breast cancer. J Immunother Cancer. https://doi.org/10.1136/jitc-2019-000173

    Article  PubMed  PubMed Central  Google Scholar 

  47. Rozenblit M, Huang R, Danziger N, et al (2020) Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers. In: San Antonio breast cancer symposium. pp PS5–08

  48. Rugo H, Loi S, Adams S et al (2020) Abstract PD1-07: exploratory analytical harmonization of PD-L1 immunohistochemistry assays in advanced triple-negative breast cancer: a retrospective substudy of IMpassion130. Cancer Res. https://doi.org/10.1158/1538-7445.SABCS19-PD1-07

    Article  Google Scholar 

  49. Carter JM, Polley M-YC, Sinnwell JP et al (2020) Abstract PD1-08: frequency, characteristics and prognostic factors of PD-L1 + triple negative breast cancer using the PD-L1 SP142 companion assay. Cancer Res. https://doi.org/10.1158/1538-7445.SABCS19-PD1-08

    Article  PubMed  PubMed Central  Google Scholar 

  50. Emens LA, Molinero L, Loi S et al (2021) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer: biomarker evaluation of the IMpassion130 study. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djab004

    Article  PubMed  PubMed Central  Google Scholar 

  51. Schmid P, Adams S, Rugo HS et al (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379:2108–2121. https://doi.org/10.1056/NEJMoa1809615

    Article  PubMed  CAS  Google Scholar 

  52. Cortes J, Cescon DW, Rugo HS et al (2020) 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. https://doi.org/10.1016/S0140-6736(20)32531-9

    Article  PubMed  Google Scholar 

  53. Schmid P, Rugo HS, Adams S et al (2019) 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. https://doi.org/10.1016/S1470-2045(19)30689-8

    Article  PubMed  Google Scholar 

  54. Rugo HS, Loi S, Adams S et al (2019) LBA20-performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): post-hoc analysis of IMpassion130. Ann Oncol 30:v858–v859. https://doi.org/10.1093/annonc/mdz394.009

    Article  Google Scholar 

  55. Miles DW, Gligorov J, André F et al (2020) LBA15 primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC). Ann Oncol 31:S1147–S1148. https://doi.org/10.1016/j.annonc.2020.08.2243

    Article  Google Scholar 

  56. Winer EP, Lipatov O, Im S-A, et al (2020) PD14-04. Contribution of tumor and immune cells to PD-L1 as a predictive biomarker in triple-negative breast cancer (TNBC): analysis from KEYNOTE-119. In: San Antonio breast cancer symposium. pp PD14–04

  57. Rugo HS, Schmid P, Cescon DW, et al (2020) GS3-01. Additional efficacy endpoints from the phase 3 KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. In: San Antonio breast cancer symposium

  58. Cortés J, Lipatov O, Im S-A et al (2019) LBA21-KEYNOTE-119: phase III study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple negative breast cancer (mTNBC). Ann Oncol 30:v859–v860. https://doi.org/10.1093/annonc/mdz394.010

    Article  Google Scholar 

  59. Loi S, Schmid P, Cortes J, et al (2020) Association between biomarkers and response to pembrolizumab in patients with metastatic triple-negative breast cancer (mTNBC): exploratory analysis from KEYNOTE-086. In: San Antonio breast cancer symposium. pp PD14–07

  60. Chia S, Bedard PL, Hilton J et al (2019) A phase Ib trial of durvalumab in combination with trastuzumab in HER2-positive metastatic breast cancer (CCTG IND.229). Oncologist. https://doi.org/10.1634/theoncologist.2019-0321

    Article  PubMed  PubMed Central  Google Scholar 

  61. Tolaney SM, Barroso-Sousa R, Keenan T et al (2020) Effect of eribulin with or without pembrolizumab on progression-free survival for patients with hormone receptor-positive, ERBB2-negative metastatic breast cancer: a randomized clinical trial. JAMA Oncol 6:1598–1605. https://doi.org/10.1001/jamaoncol.2020.3524

    Article  PubMed  Google Scholar 

  62. Loi S, Winer E, Lipatov O et al (2020) Abstract PD5–03: relationship between tumor-infiltrating lymphocytes (TILs) and outcomes in the KEYNOTE-119 study of pembrolizumab vs chemotherapy for previously treated metastatic triple-negative breast cancer (mTNBC). Cancer Res. https://doi.org/10.1158/1538-7445.SABCS19-PD5-03

    Article  PubMed  Google Scholar 

  63. Lu S, Stein JE, Rimm DL et al (2019) Comparison of biomarker modalities for predicting response to PD-1/PD-L1 checkpoint blockade: a systematic review and meta-analysis. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2019.1549

    Article  PubMed  PubMed Central  Google Scholar 

  64. Winer EP, Lipatov O, Im SA, et al (2020) Pembrolizumab versus chemotherapy for previously treated metastatic triple-negative breast cancer (KEYNOTE-119): efficacy in patients with lung or liver metastases. In: San Antonio breast cancer symposium. pp PS12–01

  65. Schmid P, Cortes J, Pusztai L et al (2020) Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382:810–821. https://doi.org/10.1056/NEJMoa1910549

    Article  PubMed  CAS  Google Scholar 

  66. Mittendorf EA, Zhang H, Barrios CH et al (2020) Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet 396:1090–1100. https://doi.org/10.1016/S0140-6736(20)31953-X

    Article  PubMed  CAS  Google Scholar 

  67. Loibl S, Untch M, Burchardi N et al (2019) A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol 30:1279–1288. https://doi.org/10.1093/annonc/mdz158

    Article  PubMed  CAS  Google Scholar 

  68. Wimberly H, Brown JR, Schalper K et al (2015) PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunol Res 3:326–332. https://doi.org/10.1158/2326-6066.CIR-14-0133

    Article  PubMed  CAS  Google Scholar 

  69. Cerbelli B, Pernazza A, Botticelli A et al (2017) PD-L1 expression in TNBC: a predictive biomarker of response to neoadjuvant chemotherapy? Biomed Res Int 2017:1750925. https://doi.org/10.1155/2017/1750925

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Gianni L, Huang C-S, Egle D et al (2020) Abstract GS3–04: pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 michelangelo randomized study. Cancer Res. https://doi.org/10.1158/1538-7445.SABCS19-GS3-04

    Article  Google Scholar 

  71. Bianchini G, Huang C-S, Egle D et al (2020) LBA13 tumour infiltrating lymphocytes (TILs), PD-L1 expression and their dynamics in the NeoTRIPaPDL1 trial. Ann Oncol 31:S1145–S1146. https://doi.org/10.1016/j.annonc.2020.08.2241

    Article  Google Scholar 

  72. Schmid P, Salgado R, Park YH et al (2020) Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: results from the phase 1b open-label, multicohort KEYNOTE-173 study. Ann Oncol 31:569–581. https://doi.org/10.1016/j.annonc.2020.01.072

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

Roberto Salgado is supported by the Breast Cancer Research Foundation (BCRF, Grant No. 17–194).

Author information

Authors and Affiliations

  1. Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia

    Peter Savas, Roberto Salgado & Sherene Loi

  2. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, 3010, Australia

    Peter Savas & Sherene Loi

  3. Department of Pathology, GZA-ZNA Hospitals, Antwerp, Belgium

    Roberto Salgado

Authors
  1. Peter Savas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberto Salgado
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sherene Loi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sherene Loi.

Ethics declarations

Conflict of interest

PS has an uncompensated consulting arrangement with Roche Genentech, and has received research funding from Roche Genentech. RS reports non-financial support from Merck and Bristol Myers Squibb; research support from Merck, Puma Biotechnology, and Roche; and personal fees from Roche for an advisory board related to a trial-research project. SL.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Savas, P., Salgado, R. & Loi, S. Seeing the forest and the tree: TILs and PD-L1 as immune biomarkers. Breast Cancer Res Treat 189, 599–606 (2021). https://doi.org/10.1007/s10549-021-06287-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-021-06287-4

Keywords

Search

Navigation