Immunometabolism

The changes that occur in intracellular metabolic pathways in immune cells during activation. Broadly, immunometabolic research records the physiological functioning of the immune system in the context of different metabolic conditions in health and disease. These studies can cover molecular and cellular aspects of immune system function in vitro, in situ, and in vivo, under different metabolic conditions. For example, highly proliferative cells such as cancer cells and activating T cells undergo metabolic reprogramming, increasing glucose uptake to shift towards aerobic glycolysis during normoxia. While aerobic glycolysis is an inefficient pathway for ATP production in quiescent cells, this so-called “Warburg effect” supports the bioenergetic and biosynthetic needs of rapidly proliferating cells.

Immunotherapy has yielded significant improvements in survival for many cancer types, but its impact on glioblastoma (GBM) has been relatively muted. There is a growing interest in understanding the role of cancer metabolism and its role in tumor growth and therapeutic response. Thus, it is equally important to consider the clinical implications of immune cell metabolism on cancer progression and implications for therapeutic development. Our objective is to present new developments in immunometabolic research that are relevant to immunotherapy development for high-grade gliomas.

Methods: A literature search and review was conducted, regarding original research articles studying metabolic pathways of immune cells in high-grade gliomas. Searches were conducted in PubMed and Embase databases on May 15 and June 13, 2022. English-language original research articles were selected and prioritized based on their inclusion of findings related to metabolic changes in myeloid and lymphoid cells in the glioma tumor microenvironment.

Key content and findings: There are many metabolic mechanisms by which immune cells in high-grade gliomas, like GBM, contribute to tumor growth and persistence via immunosuppression and high therapeutic resistance. There are also several ways that metabolic optimization has already been shown to improve immunotherapies already in clinical trials or in use, including dendritic cell vaccines and chimeric antigen receptor T cells.

Conclusions: The implications of immunometabolic research presented here should be taken into consideration in future research and immunotherapy development of high-grade gliomas for our best chances at improving patient survival. ¹⁾.

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