Journal
JOURNAL OF NEURO-ONCOLOGY
Volume 151, Issue 1, Pages 3-12Publisher
SPRINGER
DOI: 10.1007/s11060-020-03483-y
Keywords
Glioblastoma; Gbm; Glioma; Immune suppression; Immunosuppression; Immunotherapy
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Gliomas evade immune detection and destruction through mechanisms such as dysfunctional T cells and NK cells, expansion of regulatory T cells and myeloid-derived suppressor cells, M2 phenotypic transformation in macrophages/microglia, upregulation of immunosuppressive factors, tumor microenvironment hypoxia, and iatrogenic effects of immunosuppressive treatments. Future research should focus on addressing these immunosuppressive mechanisms to develop treatment options with improved survival outcomes.
Introduction The overall survival in patients with gliomas has not significantly increased in the modern era, despite advances such as immunotherapy. This is in part due to their notorious ability to suppress local and systemic immune responses, severely restricting treatment efficacy. Methods We have reviewed the preclinical and clinical evidence for immunosuppression seen throughout the disease process in gliomas. This review aims to discuss the various ways that brain tumors, and gliomas in particular, co-opt the body's immune system to evade detection and ensure tumor survival and proliferation. Results A multitude of mechanisms are discussed by which neoplastic cells evade detection and destruction by the immune system. These include tumor-induced T-cell and NK cell dysfunction, regulatory T-cell and myeloid-derived suppressor cell expansion, M2 phenotypic transformation in glioma-associated macrophages/microglia, upregulation of immunosuppressive glioma cell surface factors and cytokines, tumor microenvironment hypoxia, and iatrogenic sequelae of immunosuppressive treatments. Conclusions Gliomas create a profoundly immunosuppressive environment, both locally within the tumor and systemically. Future research should aim to address these immunosuppressive mechanisms in the effort to generate treatment options with meaningful survival benefits for this patient population.
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