TY - JOUR
T1 - Radiation and immunotherapy
T2 - Emerging mechanisms of synergy
AU - Breen, William G.
AU - Leventakos, Konstantinos
AU - Dong, Haidong
AU - Merrell, Kenneth W.
N1 - Publisher Copyright:
© Journal of Thoracic Disease. All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - Immunotherapy (IO) has become a standard treatment in patients with metastatic and locally advanced non-small cell lung cancer (NSCLC), and is now being tested in patients with early stage disease. IO agents currently in use for lung cancer target PD-1, PD-L1, and CTLA-4. While survival and tumor control have improved with IO, many patients have limited or short responses to IO. Therefore, methods to improve the systemic response to IO are needed. Radiation therapy (RT) is an integral component of lung cancer treatment, and may improve systemic response to IO by increasing antigen presentation, increasing co-stimulatory signaling, increasing T-cells recruitment, upregulating PD-L1, increasing tumor stromal lymphocyte infiltration, and altering the microenvironment. IO after definitive chemoradiation is now standard treatment in unresectable stage III NSCLC following publication of the PACIFIC clinical trial. For early stage NSCLC, IO is being investigated in conjunction with stereotactic body radiotherapy (SBRT). The benefit of adding RT to IO in patients with metastatic disease may be especially pronounced in patients with low baseline PD-L1 expression, potentially when delivered as a short course of SBRT, as supported by the PEMBRO-RT clinical trial. Current and ongoing clinical trials are evaluating the optimal radiation dose, timing, and sequencing of RT with IO.
AB - Immunotherapy (IO) has become a standard treatment in patients with metastatic and locally advanced non-small cell lung cancer (NSCLC), and is now being tested in patients with early stage disease. IO agents currently in use for lung cancer target PD-1, PD-L1, and CTLA-4. While survival and tumor control have improved with IO, many patients have limited or short responses to IO. Therefore, methods to improve the systemic response to IO are needed. Radiation therapy (RT) is an integral component of lung cancer treatment, and may improve systemic response to IO by increasing antigen presentation, increasing co-stimulatory signaling, increasing T-cells recruitment, upregulating PD-L1, increasing tumor stromal lymphocyte infiltration, and altering the microenvironment. IO after definitive chemoradiation is now standard treatment in unresectable stage III NSCLC following publication of the PACIFIC clinical trial. For early stage NSCLC, IO is being investigated in conjunction with stereotactic body radiotherapy (SBRT). The benefit of adding RT to IO in patients with metastatic disease may be especially pronounced in patients with low baseline PD-L1 expression, potentially when delivered as a short course of SBRT, as supported by the PEMBRO-RT clinical trial. Current and ongoing clinical trials are evaluating the optimal radiation dose, timing, and sequencing of RT with IO.
KW - Immunotherapy (IO)
KW - Lung cancer
KW - Metastatic disease
KW - Radiation therapy (RT)
KW - SBRT
UR - http://www.scopus.com/inward/record.url?scp=85097161312&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097161312&partnerID=8YFLogxK
U2 - 10.21037/jtd-2019-cptn-07
DO - 10.21037/jtd-2019-cptn-07
M3 - Review article
AN - SCOPUS:85097161312
SN - 2072-1439
VL - 12
SP - 7011
EP - 7023
JO - Journal of Thoracic Disease
JF - Journal of Thoracic Disease
IS - 11
ER -