Immunotherapy for Malignant Glioma: Current Status and Future Directions. (February 2020)

• Record Type: Journal Article
• Authors: Wang, Hongxiang; Xu, Tao; Huang, Qilin; Jin, Weilin; Chen, Juxiang
• Is Part Of: Trends in pharmacological sciences. Volume 41:Number 2(2020)
• Page Start: 123
• Page End: 138
• Publication Date: 2020-02
• Subjects: glioma -- immunotherapy -- checkpoint Inhibitor -- chimeric antigen receptor -- vaccine -- oncolytic virus; Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2019.12.003
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : Glioma is the most common intracranial primary malignancy, with limited treatment options and a poor overall survival (OS). Immunotherapy has been used successfully in various cancers, leading to the development of similar therapies that activate the patient's immune system to eliminate glioma. In this review, we introduce the diverse immunotherapeutic approaches available for treating glioma, highlighting the successes and challenges resulting from current clinical trials. Additionally, we emphasize the effect of multiple clinical factors on immunotherapy to help optimize individualized treatment regimens. Finally, we also highlight several novel concepts and technologies that could be used to design new and/or improve existing immunotherapies. Such approaches will delineate a new blueprint for glioma treatment. Highlights: Malignant glioma is characterized by aggressive tumor growth, high heterogeneity, intricate oncogenic pathways, and intrinsic resistance to cell death, resulting in limited treatment options and low patient OS rates. By manipulating the immune system, immunotherapeutic approaches have shown promise in achieving long-lasting tumor remission with minimal adverse effects in diverse types of cancer, including melanoma and leukemia. Several trials utilizing checkpoint inhibitors, vaccines, chimeric antigen receptor (CAR) T cells, and oncolytic viruses for treating glioma reveal obstacles to achieving sustained responses, possibly due to a highly immunosuppressive tumor milieu, few and/or exhausted tumor-infiltrating lymphocytes, and a deficiency of specific and immunogenic tumor antigens. Various clinical factors, including corticosteroids, isocitrate dehydrogenase (IDH) mutations, age, gender, obesity, and gut microbiota, may have an important impact on the efficacy of immunotherapy in patients with glioma, enabling the optimal design of individualized treatment. The availability of data relating to the targeting of glioma stem cells, remodeling of the glioma microenvironment, CAR–natural killer cell interactions, shock and kill strategies, optogenetic immunomodulation, organoid use, and liquid biopsies of cerebrospinal fluid provide novel research directions for the development of glioma immunotherapy with optimal efficiency.