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      Analyzing the impact of metabolism on immune cells in tumor microenvironment to promote the development of immunotherapy

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          Abstract

          Tumor metabolism and tumor immunity are inextricably linked. Targeting the metabolism of tumors is a point worth studying in tumor immunotherapy. Recently, the influence of the metabolism of tumors and immune cells on the occurrence, proliferation, metastasis, and prognosis of tumors has attracted more attention. Tumor tissue forms a specific tumor microenvironment (TME). In addition to tumor cells, there are also immune cells, stromal cells, and other cells in TME. To adapt to the environment, tumor cells go through the metabolism reprogramming of various substances. The metabolism reprogramming of tumor cells may further affect the formation of the tumor microenvironment and the function of a variety of cells, especially immune cells, eventually promoting tumor development. Therefore, it is necessary to study the metabolism of tumor cells and its effects on immune cells to guide tumor immunotherapy. Inhibiting tumor metabolism may restore immune balance and promote the immune response in tumors. This article will describe glucose metabolism, lipid metabolism, amino acid metabolism, and immune cells in tumors. Besides, the impact of metabolism on the immune cells in TME is also discussed for analyzing and exploring tumor immunotherapy.

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          Most cited references101

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          Dysregulated pH: a perfect storm for cancer progression.

          Although cancer is a diverse set of diseases, cancer cells share a number of adaptive hallmarks. Dysregulated pH is emerging as a hallmark of cancer because cancers show a 'reversed' pH gradient with a constitutively increased intracellular pH that is higher than the extracellular pH. This gradient enables cancer progression by promoting proliferation, the evasion of apoptosis, metabolic adaptation, migration and invasion. Several new advances, including an increased understanding of pH sensors, have provided insight into the molecular basis for pH-dependent cell behaviours that are relevant to cancer cell biology. We highlight the central role of pH sensors in cancer cell adaptations and suggest how dysregulated pH could be exploited to develop cancer-specific therapeutics.
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            Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells

            Metabolic reprogramming is a hallmark of cancer. Here, we demonstrate that tumour-associated macrophages (TAMs) enhance the aerobic glycolysis and apoptotic resistance of breast cancer cells via the extracellular vesicle (EV) transmission of a myeloid-specific lncRNA, HIF-1α-stabilizing long noncoding RNA (HISLA). Mechanistically, HISLA blocks the interaction of PHD2 and HIF-1α to inhibit the hydroxylation and degradation of HIF-1α. Reciprocally, lactate released from glycolytic tumour cells upregulates HISLA in macrophages, constituting a feed-forward loop between TAMs and tumour cells. Blocking EV-transmitted HISLA inhibits the glycolysis and chemoresistance of breast cancer in vivo. Clinically, HISLA expression in TAMs is associated with glycolysis, poor chemotherapeutic response and shorter survival of patients with breast cancer. Our study highlights the potential of lncRNAs as signal transducers that are transmitted between immune and tumour cells via EVs to promote cancer aerobic glycolysis.
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              Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages

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                Author and article information

                Contributors
                Role:
                Role:
                Role: Role:
                URI : https://loop.frontiersin.org/people/2005351Role: Role:
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                08 January 2024
                2023
                : 14
                : 1307228
                Affiliations
                [1] Department of Gynecology and Obstetrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second Hospital, Sichuan University , Chengdu, China
                Author notes

                Edited by: Asif Raza, Penn State Milton S. Hershey Medical Center, United States

                Reviewed by: Anna Fakhardo, The Pennsylvania State University, United States

                Hamid Aria, Isfahan University of Medical Sciences, Iran

                Seyma Demirsoy, The Pennsylvania State University, United States

                *Correspondence: Xiaorong Qi, qixiaorong11@ 123456163.com
                Article
                10.3389/fimmu.2023.1307228
                10804850
                38264667
                dfae9083-d5e7-41d8-a79e-b9a53ef2ed4c
                Copyright © 2024 Long, Shi, He and Qi

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 October 2023
                : 18 December 2023
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 101, Pages: 15, Words: 10674
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Sichuan Province Tianfu Qingcheng Program Foundation, Grant/Award(No. KZ258) and Sichuan Science and Technology Program (No. 22ZDYF2119).
                Categories
                Immunology
                Review
                Custom metadata
                Cancer Immunity and Immunotherapy

                Immunology
                metabolism reprogramming,tumor microenvironment,immunotherapy,glucose metabolism,lipid metabolism,amino acid metabolism

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