TY - JOUR
T1 - Combining radiation therapy with immune checkpoint blockade for central nervous system malignancies
AU - D'Souza, Neil M.
AU - Fang, Penny
AU - Logan, Jennifer
AU - Yang, Jinzhong
AU - Jiang, Wen
AU - Li, Jing
N1 - Publisher Copyright:
© 2016 D'Souza, Fang, Logan, Yang, Jiang and Li.
PY - 2016/10/7
Y1 - 2016/10/7
N2 - Malignancies of the central nervous system (CNS), particularly glioblastoma and brain metastases from a variety of disease sites, are difficult to treat despite advances in multimodality approaches consisting of surgery, chemotherapy, and radiation therapy (RT). Recent successes of immunotherapeutic strategies including immune checkpoint blockade (ICB) via anti-PD-1 and anti-CTLA-4 antibodies against aggressive cancers, such as melanoma, non-small cell lung cancer, and renal cell carcinoma, have presented an exciting opportunity to translate these strategies for CNS malignancies. Moreover, via both localized cytotoxicity and systemic proinflammatory effects, the role of RT in enhancing antitumor immune response and, therefore, promoting tumor control is being re-examined, with several preclinical and clinical studies demonstrating potential synergistic effect of RT with ICB in the treatment of primary and metastatic CNS tumors. In this review, we highlight the preclinical evidence supporting the immunomodulatory effect of RT and discuss the rationales for its combination with ICB to promote antitumor immune response. We then outline the current clinical experience of combining RT with ICB in the treatment of multiple primary and metastatic brain tumors. Finally, we review advances in characterizing and modifying tumor radioimmunotherapy responses using biomarkers and microRNA (miRNA) that may potentially be used to guide clinical decision-making in the near future.
AB - Malignancies of the central nervous system (CNS), particularly glioblastoma and brain metastases from a variety of disease sites, are difficult to treat despite advances in multimodality approaches consisting of surgery, chemotherapy, and radiation therapy (RT). Recent successes of immunotherapeutic strategies including immune checkpoint blockade (ICB) via anti-PD-1 and anti-CTLA-4 antibodies against aggressive cancers, such as melanoma, non-small cell lung cancer, and renal cell carcinoma, have presented an exciting opportunity to translate these strategies for CNS malignancies. Moreover, via both localized cytotoxicity and systemic proinflammatory effects, the role of RT in enhancing antitumor immune response and, therefore, promoting tumor control is being re-examined, with several preclinical and clinical studies demonstrating potential synergistic effect of RT with ICB in the treatment of primary and metastatic CNS tumors. In this review, we highlight the preclinical evidence supporting the immunomodulatory effect of RT and discuss the rationales for its combination with ICB to promote antitumor immune response. We then outline the current clinical experience of combining RT with ICB in the treatment of multiple primary and metastatic brain tumors. Finally, we review advances in characterizing and modifying tumor radioimmunotherapy responses using biomarkers and microRNA (miRNA) that may potentially be used to guide clinical decision-making in the near future.
KW - Brain metastases
KW - Brain neoplasms
KW - CTLA-4
KW - Glioblastoma
KW - Immune checkpoint blockade
KW - Immunotherapy
KW - PD-1
KW - Radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=84997416758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84997416758&partnerID=8YFLogxK
U2 - 10.3389/fonc.2016.00212
DO - 10.3389/fonc.2016.00212
M3 - Short survey
C2 - 27774435
AN - SCOPUS:84997416758
SN - 2234-943X
VL - 6
JO - Frontiers in Oncology
JF - Frontiers in Oncology
IS - OCT
M1 - 212
ER -