Immunomodulatory Effects of Radiotherapy
Abstract
:1. Introduction
2. Radiation as Therapy
2.1. Conventional Photon Radiation Therapy
2.2. Stereotactic Body Radiotherapy (SBRT)
2.3. Charged Particle Therapy
2.3.1. Proton Therapy
2.3.2. Carbon Ion Therapy
3. Nature of DNA Lesions and the Mechanism of DNA Repair
3.1. DNA Damage and DNA Repair are the Sine Qua Non of Radiation Injury
3.2. Charged Particles Induce Clustered DNA Double-Strand Breaks
3.3. Non-Homologous End Joining (NHEJ) is Required for Processing Simple DSBs
3.4. The Homologous Recombination Repair Pathway is Required for Processing Clustered DSBs
3.5. Repairing Non-DSBs in Clustered DNA Damage: Base Excision Repair (BER)
4. Radiotherapy and Immune Signaling
4.1. Radiation and Innate Immune Signaling
4.2. Radiation and Adaptive Immune Signaling
4.3. Radiation and Cancer Vaccines
4.4. Radiation and Tumor Antigens
4.5. Trial Studies Combining RT with Immunomodulators
5. Radiotherapy and Abscopal Effects
6. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
APC | Antigen presenting cell |
AIM2 | Absent in melanoma 2 |
BER | Base excision repair |
CCR2 | Chemokine receptor 2 |
CGA | Cancer-germline antigen |
cGAS | Cyclic GMP-AMP synthase |
CIRT | Carbon ion radiotherapy |
CTL | Cytotoxic T lymphocytes |
DAMP | Damage-associated molecular pattern |
DC | Dendritic cell |
DDR | DNA damage response |
DSB | DNA double-strand break |
HR | Homologous recombination |
IFN | Interferon |
IMRT | Intensity-modulated radiotherapy |
IRF3 | Interferon regulatory transcription factor 3 |
LEM | Local effects model |
LET | Linear energy transfer |
MDSC | Myeloid-derived suppressor cell |
NHEJ | Non-homologous end joining |
NSCLC | Non-small cell lung cancer |
PET | Positron emission tomography |
RBE | Relative biological effectiveness |
RT | Radiotherapy |
SBRT | Stereotactic body radiation therapy |
SSB | Single-strand break |
STING | Stimulator of interferon gene |
TCR | T cell receptor |
TNF | Tumor necrosis factor |
TME | Tumor microenvironment |
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Cancer Type | Radiotherapy | Type of Study | Beneficial Effects | Reference(s) |
---|---|---|---|---|
Prostate | Proton | Trial study unknown | Better target delivery of radiation, low exit dose | [27,28,29] |
[30,31,32] | ||||
Head and Neck | Proton | Trial study unknown | Less radiation-induced tissue damage | [33,34,35] |
Better survival | [36] | |||
Decreased rates of tube feeding dependency, better quality of life | [37] | |||
Non-Small Cell Lung Cancer | Proton vs. IMRT | Randomized study | Better dosimetric indices for heart sparing, and the risk of pneumonitis decreased over the duration of the study | [38] |
Liver and Colon | Proton vs. SBRT | Trial study unknown | Longer survival than SBRT, spares more normal liver cells from radiation damage than treating with conventional RT | [39,40,41] |
Esophageal | Proton vs. IMRT | Randomized Phase II | The mean total toxicity burden was considerably lower with protons than with IMRT | [42] |
Brain (Adult) | Proton | Trial study unknown | Significantly reduced the side effects and better neurocognition over time after treatment | [43,44,45,46] |
Brain (Pediatric) | Proton vs. Photon | Trial study unknown | Spared more surrounding normal tissue; reduced side effects and increased five-year survival rates (72–100%) | [32,47,48,49,50] |
Safer to deliver high dose of radiation and better neurocognition | [44,45,46,51] |
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Kumari, S.; Mukherjee, S.; Sinha, D.; Abdisalaam, S.; Krishnan, S.; Asaithamby, A. Immunomodulatory Effects of Radiotherapy. Int. J. Mol. Sci. 2020, 21, 8151. https://doi.org/10.3390/ijms21218151
Kumari S, Mukherjee S, Sinha D, Abdisalaam S, Krishnan S, Asaithamby A. Immunomodulatory Effects of Radiotherapy. International Journal of Molecular Sciences. 2020; 21(21):8151. https://doi.org/10.3390/ijms21218151
Chicago/Turabian StyleKumari, Sharda, Shibani Mukherjee, Debapriya Sinha, Salim Abdisalaam, Sunil Krishnan, and Aroumougame Asaithamby. 2020. "Immunomodulatory Effects of Radiotherapy" International Journal of Molecular Sciences 21, no. 21: 8151. https://doi.org/10.3390/ijms21218151