Combining PARP Inhibition, Radiation, and Immunotherapy: A Possible Strategy to Improve the Treatment of Cancer?
Abstract
:1. Introduction
1.1. The Immune System in Tumor Control
1.2. Combination of Treatments with Immunotherapies
2. Interactions and Synergy between PARPis and Immunotherapies in Tumor Control
2.1. PARPis as a Cytotoxic Treatment
2.2. PARPis and the Antitumor Immune Response
2.2.1. Anti-CTLA-4 and PARPis
2.2.2. Anti-PDL-1/PD-1 and PARPis
3. Immunotherapy and Radiation: A Synergistic Effect Mediated by Cytotoxic Lymphocytes
3.1. Ionizing Radiation Induces an Antitumor Immune Response Mediated by Cytotoxic Lymphocytes
3.2. Radiation and Immunotherapies Can Synergize to Control the Tumor
3.3. Radiation-Induced Immunosuppressive Effects Can Be Reversed with Immunotherapy
3.4. Inducing an Antitumor Immune Response with Proton or Carbon Ion Radiation
4. PARPis and Ionizing Radiation: A Promising Combination Therapy
5. Conclusions and Perspectives: A Rationale for Combining PARPis, Ionizing Radiation, and Immunotherapy
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
APC | Antigen-presenting cell |
BRCA | BReast CAncer |
CCL2 | Chemokine (C-C motif) ligand 2 |
CCL5 | Chemokine (C-C motif) ligand 5 |
CTLs | specific activated CD8+ lymphocytes against tumor antigens |
CTLA-4 | Cytotoxic T lymphocyte-associated antigen 4 |
CXCL-16 | Chemokine (C-X-C motif) ligand 16 |
CXCL-10 | Chemokine (C-X-C motif) ligand 10 |
DC | Dendritic cell |
DSB | Double-strand break |
GBM | Glioblastoma |
Gy | Gray |
HMGB1 | High-mobility group box 1 |
MDSC | Myeloid-derived suppressor cells |
MHC | Major histocompatibility complex |
NSCLC | Non-small-cell lung cancer |
PARP | Poly(ADP-ribose) polymerase |
PARPi | PARP inhibitor |
PD-1 | Programmed cell death protein 1 |
PDL-1 | Programmed cell death ligand 1 |
TAA | Tumor-associated antigen |
TCR | T cell receptor |
TIL | Tumor-infiltrating lymphocyte |
TNBC | Triple-negative breast cancer |
TMZ | Temozolomide |
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Césaire, M.; Thariat, J.; Candéias, S.M.; Stefan, D.; Saintigny, Y.; Chevalier, F. Combining PARP Inhibition, Radiation, and Immunotherapy: A Possible Strategy to Improve the Treatment of Cancer? Int. J. Mol. Sci. 2018, 19, 3793. https://doi.org/10.3390/ijms19123793
Césaire M, Thariat J, Candéias SM, Stefan D, Saintigny Y, Chevalier F. Combining PARP Inhibition, Radiation, and Immunotherapy: A Possible Strategy to Improve the Treatment of Cancer? International Journal of Molecular Sciences. 2018; 19(12):3793. https://doi.org/10.3390/ijms19123793
Chicago/Turabian StyleCésaire, Mathieu, Juliette Thariat, Serge M. Candéias, Dinu Stefan, Yannick Saintigny, and François Chevalier. 2018. "Combining PARP Inhibition, Radiation, and Immunotherapy: A Possible Strategy to Improve the Treatment of Cancer?" International Journal of Molecular Sciences 19, no. 12: 3793. https://doi.org/10.3390/ijms19123793