Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas

Jean Philippe Nesseler*, Dorthe Schaue, William H. McBride, Mi Heon Lee, Tania Kaprealian, Simone P. Niclou, Philippe Nickers

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)268-282
Number of pages15
JournalAdvances in Radiation Oncology
Volume4
Issue number2
DOIs
Publication statusPublished - 1 Apr 2019

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