Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.676301
Keywords
glioblastoma; brain cancer; immunotherapy; tumor microenvironment; resistance to therapy
Categories
Funding
- Brain Tumor Funders' Collaborative (BTFC)
- Canada Foundation for Innovation (CFI-JELF) [37488]
- Tier II Canada Research Chair in Tumor Micro environment Research
- Department of Physiology, McGill University
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Glioblastoma, a highly lethal brain cancer, has brought immunotherapy to the forefront of research, but faces challenges such as resistance, tumor heterogeneity, and immunosuppressive environments. Despite these difficulties, there is active pursuit of more effective immunotherapies for glioblastoma.
Glioblastoma is a highly lethal brain cancer with a median survival rate of less than 15 months when treated with the current standard of care, which consists of surgery, radiotherapy and chemotherapy. With the recent success of immunotherapy in other aggressive cancers such as advanced melanoma and advanced non-small cell lung cancer, glioblastoma has been brought to the forefront of immunotherapy research. Resistance to therapy has been a major challenge across a multitude of experimental candidates and no immunotherapies have been approved for glioblastoma to-date. Intra- and inter-tumoral heterogeneity, an inherently immunosuppressive environment and tumor plasticity remain barriers to be overcome. Moreover, the unique tissue-specific interactions between the central nervous system and the peripheral immune system present an additional challenge for immune-based therapies. Nevertheless, there is sufficient evidence that these challenges may be overcome, and immunotherapy continues to be actively pursued in glioblastoma. Herein, we review the primary ongoing immunotherapy candidates for glioblastoma with a focus on immune checkpoint inhibitors, myeloid-targeted therapies, vaccines and chimeric antigen receptor (CAR) immunotherapies. We further provide insight on mechanisms of resistance and how our understanding of these mechanisms may pave the way for more effective immunotherapeutics against glioblastoma.
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