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Metabolic Reprogramming of the Tumor Microenvironment to Enhance Response to Immunotherapy
Seon Ah Lim1,* (Professor)
1Department of Life Science, Ewha Womans University, Seoul 03760,
2Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, Korea
Immunotherapy represents a promising treatment strategy for targeting various tumor types. However, the overall response rate is low due to the tumor microenvironment (TME). In the TME, numerous distinct factors actively induce immunosuppression, restricting the efficacy of anticancer immune reactions. Recently, metabolic reprogramming of tumors has been recognized for its role in modulating the tumor microenvironment to enhance immune cell responses in the TME. Furthermore, recent elucidations underscore the critical role of metabolic limitations imposed by the tumor microenvironment on the effectiveness of antitumor immune cells, guiding the development of novel immunotherapeutic approaches. Achieving a comprehensive understanding of metabolic requirements of both cancer and immune cells within the TME is pivotal. This insight not only aids in acknowledging current limitations of clinical practices, but also significantly shapes the trajectory of future research endeavors in the domain of cancer immunotherapy. In addition, therapeutic interventions targeting metabolic limitations have exhibited promising potential as combinatory treatments across diverse cancer types. In this review, we first discuss metabolic barriers in the TME. Second, we explore how immune responses are regulated by metabolites. Finally, we will review the current strategy for targeting metabolism to not simply inhibit tumor growth, but also enhance antitumor immune responses. Thus, we could suggest potent combination therapy for improving responses to immunotherapy with metabolic inhibitors.
Abstract, Accepted Manuscript(in press) [Submitted on February 26, 2024, Accepted on June 21, 2024]
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