[en] 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.
Disciplines :
Oncology
Author, co-author :
Nesseler, Jean Philippe; Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, California.
Schaue, Dorthe; Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, California.
McBride, William H; Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, California.
Lee, Mi-Heon; Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, California.
Kaprealian, Tania; Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, California.
NICLOU, Simone P. ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) ; NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg City, Luxembourg.
Nickers, Philippe; Department of Radiation Oncology, Centre François Baclesse, Esch-sur-Alzette, Luxembourg.
External co-authors :
yes
Language :
English
Title :
Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas.
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