TY - JOUR
T1 - Harnessing and optimizing the interplay between immunotherapy and radiotherapy to improve survival outcomes
AU - Mujoo, Kalpana
AU - Hunt, Clayton R.
AU - Pandita, Raj K.
AU - Ferrari, Mauro
AU - Krishnan, Sunil
AU - Cooke, John P.
AU - Hahn, Stephen
AU - Pandita, Tej K.
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/8
Y1 - 2018/8
N2 - In the past, radiotherapy was primarily used to control local disease, but recent technological advances in accurate, high-dose ionizing radiation (IR) delivery have not only increased local tumor control but in some cases reduced metastatic burden. These "off target" therapeutic effects of IR at nonirradiated tumor sites, also known as abscopal effects, are thought to be mediated by tumor antigen–primed T cells that travel to metastatic sites and promote tumor regression. Similarly, early indications reveal that IR in combination with immune checkpoint inhibitors, such as ipilimumab (anti–CTLA-4) and nivolumab (anti–PD-1), can provide superior therapeutic responses. These observations suggest that local radiotherapy results in altered gene expression, exposure of new antigens, or cell death that can interact with immunotherapy. As such, radiotherapy enhancement of immune responses offers a promising synergy with the potential for substantial clinical benefit. This review focuses on the biology that underlies the mechanisms for the interaction between radiation-induced tumor cell death and enhanced immunologic response.
AB - In the past, radiotherapy was primarily used to control local disease, but recent technological advances in accurate, high-dose ionizing radiation (IR) delivery have not only increased local tumor control but in some cases reduced metastatic burden. These "off target" therapeutic effects of IR at nonirradiated tumor sites, also known as abscopal effects, are thought to be mediated by tumor antigen–primed T cells that travel to metastatic sites and promote tumor regression. Similarly, early indications reveal that IR in combination with immune checkpoint inhibitors, such as ipilimumab (anti–CTLA-4) and nivolumab (anti–PD-1), can provide superior therapeutic responses. These observations suggest that local radiotherapy results in altered gene expression, exposure of new antigens, or cell death that can interact with immunotherapy. As such, radiotherapy enhancement of immune responses offers a promising synergy with the potential for substantial clinical benefit. This review focuses on the biology that underlies the mechanisms for the interaction between radiation-induced tumor cell death and enhanced immunologic response.
UR - http://www.scopus.com/inward/record.url?scp=85048164263&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048164263&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-17-0743
DO - 10.1158/1541-7786.MCR-17-0743
M3 - Review article
C2 - 29592896
AN - SCOPUS:85048164263
SN - 1541-7786
VL - 16
SP - 1209
EP - 1214
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 8
ER -