TY - JOUR
T1 - Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas
AU - Nesseler, Jean Philippe
AU - Schaue, Dorthe
AU - McBride, William H.
AU - Lee, Mi Heon
AU - Kaprealian, Tania
AU - Niclou, Simone P.
AU - Nickers, Philippe
N1 - Funding Information:
Sources of support: Funding was granted by the National Institutes of Health to Dr. Dorthe Schaue (1R01CA191234-01).
Publisher Copyright:
© 2018 The Author(s)
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Purpose: Glioblastoma (GBM) remains an incurable disease despite extensive treatment with surgical resection, irradiation, and temozolomide. In line with many other forms of aggressive cancers, GBM is currently under consideration as a target for immunotherapy. However, GBM tends to be nonimmunogenic and exhibits a microenvironment with few or no effector T cells, a relatively low nonsynonymous somatic mutational load, and a low predicted neoantigen burden. GBM also exploits a multitude of immunosuppressive strategies. Methods and Materials: A number of immunotherapeutic approaches have been tested with disappointing results. A rationale exists to combine immunotherapy and radiation therapy, which can induce an immunogenic form of cell death with T-cell activation and tumor infiltration. Results: Various immunotherapy agents, including immune checkpoint modulators, transforming growth factor beta receptor inhibitors, and indoleamine-2,3-dioxygenase inhibitors, have been evaluated with irradiation in preclinical GBM models, with promising results, and are being further tested in clinical trials. Conclusions: This review aims to present the basic rationale behind this emerging complementary therapeutic approach in GBM, appraise the current preclinical and clinical data, and discuss the future challenges in improving the antitumor immune response.
AB - Purpose: Glioblastoma (GBM) remains an incurable disease despite extensive treatment with surgical resection, irradiation, and temozolomide. In line with many other forms of aggressive cancers, GBM is currently under consideration as a target for immunotherapy. However, GBM tends to be nonimmunogenic and exhibits a microenvironment with few or no effector T cells, a relatively low nonsynonymous somatic mutational load, and a low predicted neoantigen burden. GBM also exploits a multitude of immunosuppressive strategies. Methods and Materials: A number of immunotherapeutic approaches have been tested with disappointing results. A rationale exists to combine immunotherapy and radiation therapy, which can induce an immunogenic form of cell death with T-cell activation and tumor infiltration. Results: Various immunotherapy agents, including immune checkpoint modulators, transforming growth factor beta receptor inhibitors, and indoleamine-2,3-dioxygenase inhibitors, have been evaluated with irradiation in preclinical GBM models, with promising results, and are being further tested in clinical trials. Conclusions: This review aims to present the basic rationale behind this emerging complementary therapeutic approach in GBM, appraise the current preclinical and clinical data, and discuss the future challenges in improving the antitumor immune response.
UR - http://www.scopus.com/inward/record.url?scp=85058700986&partnerID=8YFLogxK
U2 - 10.1016/j.adro.2018.11.005
DO - 10.1016/j.adro.2018.11.005
M3 - Review article
AN - SCOPUS:85058700986
SN - 2452-1094
VL - 4
SP - 268
EP - 282
JO - Advances in Radiation Oncology
JF - Advances in Radiation Oncology
IS - 2
ER -