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Metabolic reprogramming of the tumor microenvironment to enhance immunotherapy

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초록

Immunotherapy represents a promising treatment strategy fortargeting various tumor types. However, the overall responserate is low due to the tumor microenvironment (TME). In theTME, numerous distinct factors actively induce immunosuppression,restricting the efficacy of anticancer immune reactions. Recently, metabolic reprogramming of tumors has been recognizedfor its role in modulating the tumor microenvironmentto enhance immune cell responses in the TME. Furthermore,recent elucidations underscore the critical role of metaboliclimitations imposed by the tumor microenvironment on theeffectiveness of antitumor immune cells, guiding the developmentof novel immunotherapeutic approaches. Hence, achievinga comprehensive understanding of the metabolic requirementsof both cancer and immune cells within the TME is pivotal. Thisinsight not only aids in acknowledging the current limitations ofclinical practices but also significantly shapes the trajectory offuture research endeavors in the domain of cancer immunotherapy. In addition, therapeutic interventions targeting metaboliclimitations have exhibited promising potential as combinatorytreatments across diverse cancer types. In this review, we firstdiscuss the metabolic barriers in the TME. Second, we explorehow the immune response is regulated by metabolites. Finally,we will review the current strategy for targeting metabolism tonot simply inhibit tumor growth but also enhance antitumorimmune responses. Thus, we could suggest potent combinationtherapy for improving immunotherapy with metabolic inhibitors.

Abstract

Immunotherapy represents a promising treatment strategy fortargeting various tumor types. However, the overall responserate is low due to the tumor microenvironment (TME). In theTME, numerous distinct factors actively induce immunosuppression,restricting the efficacy of anticancer immune reactions. Recently, metabolic reprogramming of tumors has been recognizedfor its role in modulating the tumor microenvironmentto enhance immune cell responses in the TME. Furthermore,recent elucidations underscore the critical role of metaboliclimitations imposed by the tumor microenvironment on theeffectiveness of antitumor immune cells, guiding the developmentof novel immunotherapeutic approaches. Hence, achievinga comprehensive understanding of the metabolic requirementsof both cancer and immune cells within the TME is pivotal. Thisinsight not only aids in acknowledging the current limitations ofclinical practices but also significantly shapes the trajectory offuture research endeavors in the domain of cancer immunotherapy. In addition, therapeutic interventions targeting metaboliclimitations have exhibited promising potential as combinatorytreatments across diverse cancer types. In this review, we firstdiscuss the metabolic barriers in the TME. Second, we explorehow the immune response is regulated by metabolites. Finally,we will review the current strategy for targeting metabolism tonot simply inhibit tumor growth but also enhance antitumorimmune responses. Thus, we could suggest potent combinationtherapy for improving immunotherapy with metabolic inhibitors.

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