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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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Review Article

Manipulating Metabolic Alterations and their Consequences to Unleash the Potential of Antitumor Immunotherapy

Author(s): Xuanyu Zhu, Longfei Zhu and Yan Wu*

Volume 23, Issue 9, 2022

Published on: 19 September, 2022

Page: [585 - 601] Pages: 17

DOI: 10.2174/1389203723666220620161742

Price: $65

Abstract

Cellular metabolic reprogramming driven by oncogenic mutations is considered as a hallmark in the development of malignant cells, and has been a focus over the past decade. A common theme emerging from these metabolic alterations is that tumor cells can acquire necessary nutrients from a nutrient-limited microenvironment and utilize them to sustain growth and unrestrained cellular division. However, this significant metabolic flexibility and the hostile microenvironment caused by the insufficient vascular exchange, depletion of nutrients, hypoxia, and accumulation of waste products, can inhibit the metabolism and immune activity of tumor-infiltrating lymphocytes and impose barriers to effective antitumor immunotherapies. In this perspective, we review the classical alterations in tumorigenesis- associated metabolic reprogramming and examine the functional contribution of these aberrant metabolisms to the establishment and maintenance of an immunosuppressive microenvironment. Furthermore, we explore the possible approaches to targeting on these metabolic pathways to achieve antitumor immunotherapy, as well as some hypothetical or ongoing combination therapeutic strategies that could, to a certain extent, biologically rationalize and broaden the utility of immune checkpoint inhibitors. Ultimately, we elucidate some dietary modifications that can limit tumor-specific nutritional requirements and maximize the cytotoxicity of other antineoplastic drugs.

Keywords: Tumor metabolic reprogramming, T-cell, immune response, antitumor immunotherapy, nutrition, diet intervention.

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