TY - JOUR
T1 - The intersection of radiotherapy and immunotherapy
T2 - Mechanisms and clinical implications
AU - Spiotto, Michael
AU - Fu, Yang Xin
AU - Weichselbaum, Ralph R.
N1 - Funding Information:
Given the depth of this radiotherapy and immunotherapy review, we regret any oversight in failing to cite all works. We thank A. K. Huser for thoughtful research, writing, and editing assistance. This work was supported in part by the Ludwig Center for Metastasis Research and NIH grant R21 CA195075A (to R.R.W.), a Burroughs Wellcome Career Award for Medical Scientists (1010964; to M.S.), and the Fanconi Anemia Research Fund (to M.S.).
Publisher Copyright:
2016 © The Authors. All Rights Reserved.
PY - 2016
Y1 - 2016
N2 - By inducing DNA damage, radiotherapy both reduces tumor burden and enhances antitumor immunity. Here, we review the mechanisms by which radiation induces antitumor immune responses, which can be augmented using immunotherapies to facilitate tumor regression. Radiotherapy increases inflammation in tumors by activating the nuclear factor kB and the type I interferon response pathways to induce expression of proinflammatory cytokines. This inflammation coupled with antigen release from irradiated cells facilitates dendritic cell maturation and cross-presentation of tumor antigens to prime tumor-specific T cell responses. Radiation also sensitizes tumors to these T cell responses by enhancing T cell infiltration into tumors and the recognition of both malignant cancer cells and nonmalignant stroma that present cognate antigen. Yet, these antitumor immune responses may be blunted by several mechanisms, including regulatory T cells and checkpoint molecules that promote T cell tolerance and exhaustion. Consequently, the combination of immunotherapy using vaccines and/or checkpoint inhibitors with radiation demonstrates early clinical potential. Overall, this Review will provide a global view on how radiation and the immune system converge to target cancers and the early attempts to exploit this synergy in clinical practice.
AB - By inducing DNA damage, radiotherapy both reduces tumor burden and enhances antitumor immunity. Here, we review the mechanisms by which radiation induces antitumor immune responses, which can be augmented using immunotherapies to facilitate tumor regression. Radiotherapy increases inflammation in tumors by activating the nuclear factor kB and the type I interferon response pathways to induce expression of proinflammatory cytokines. This inflammation coupled with antigen release from irradiated cells facilitates dendritic cell maturation and cross-presentation of tumor antigens to prime tumor-specific T cell responses. Radiation also sensitizes tumors to these T cell responses by enhancing T cell infiltration into tumors and the recognition of both malignant cancer cells and nonmalignant stroma that present cognate antigen. Yet, these antitumor immune responses may be blunted by several mechanisms, including regulatory T cells and checkpoint molecules that promote T cell tolerance and exhaustion. Consequently, the combination of immunotherapy using vaccines and/or checkpoint inhibitors with radiation demonstrates early clinical potential. Overall, this Review will provide a global view on how radiation and the immune system converge to target cancers and the early attempts to exploit this synergy in clinical practice.
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U2 - 10.1126/sciimmunol.aag1266
DO - 10.1126/sciimmunol.aag1266
M3 - Article
C2 - 28018989
AN - SCOPUS:85041734576
SN - 2470-9468
VL - 1
JO - Science Immunology
JF - Science Immunology
IS - 3
M1 - eaag1266
ER -