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      Impact of Drp1-Mediated Mitochondrial Dynamics on T Cell Immune Modulation

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          Abstract

          In recent years, various breakthroughs have been made in tumor immunotherapy that have contributed to prolonging the survival of tumor patients. However, only a subset of patients respond to immunotherapy, which limits its use. One reason for this is that the tumor microenvironment (TME) hinders the migration and infiltration of T cells and affects their continuous functioning, resulting in an exhausted phenotype. Therefore, clarifying the mechanism by which T cells become exhausted is of significance for improving the efficacy of immunotherapy. Several recent studies have shown that mitochondrial dynamics play an important role in the immune surveillance function of T cells. Dynamin-related protein 1 (Drp1) is a key protein that mediates mitochondrial fission and maintains the mitochondrial dynamic network. Drp1 regulates various activities of T cells in vivo by mediating the activation of a series of pathways. In addition, abnormal mitochondrial dynamics were observed in exhausted T cells in the TME. As a potential target for immunotherapy, in this review, we describe in detail how Drp1 regulates various physiological functions of T cells and induces changes in mitochondrial dynamics in the TME, providing a theoretical basis for further research.

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          Most cited references100

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          A guide to cancer immunotherapy: from T cell basic science to clinical practice

          The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation. We highlight clinical trials that demonstrate therapeutic efficacy and toxicities associated with each class of drug. Finally, we summarize emerging therapies and emphasize the yet to be elucidated questions and future promise within the field of cancer immunotherapy.
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            Molecular and cellular insights into T cell exhaustion.

            In chronic infections and cancer, T cells are exposed to persistent antigen and/or inflammatory signals. This scenario is often associated with the deterioration of T cell function: a state called 'exhaustion'. Exhausted T cells lose robust effector functions, express multiple inhibitory receptors and are defined by an altered transcriptional programme. T cell exhaustion is often associated with inefficient control of persisting infections and tumours, but revitalization of exhausted T cells can reinvigorate immunity. Here, we review recent advances that provide a clearer molecular understanding of T cell exhaustion and reveal new therapeutic targets for persisting infections and cancer.
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              Accessories to the crime: functions of cells recruited to the tumor microenvironment.

              Mutationally corrupted cancer (stem) cells are the driving force of tumor development and progression. Yet, these transformed cells cannot do it alone. Assemblages of ostensibly normal tissue and bone marrow-derived (stromal) cells are recruited to constitute tumorigenic microenvironments. Most of the hallmarks of cancer are enabled and sustained to varying degrees through contributions from repertoires of stromal cell types and distinctive subcell types. Their contributory functions to hallmark capabilities are increasingly well understood, as are the reciprocal communications with neoplastic cancer cells that mediate their recruitment, activation, programming, and persistence. This enhanced understanding presents interesting new targets for anticancer therapy. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                31 March 2022
                2022
                : 13
                : 873834
                Affiliations
                [1] Department of Oncology, Shengjing Hospital of China Medical University , Shenyang, China
                Author notes

                Edited by: Ariel Quintana-Gonzalez, Moffitt Cancer Center, United States

                Reviewed by: Leonardo M.R. Ferreira, Medical University of South Carolina, United States; Nicole M. Chapman, St. Jude Children’s Research Hospital, United States

                *Correspondence: Jietao Ma, majt@ 123456sj-hospital.org

                This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.873834
                9008543
                35432303
                62c7b2e3-9490-4412-a704-2a10c6ea63e3
                Copyright © 2022 Song, Yi, Gao, Sun, Wu, Zhang, Huang, Han and Ma

                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
                : 11 February 2022
                : 11 March 2022
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 100, Pages: 10, Words: 4528
                Categories
                Immunology
                Review

                Immunology
                dynamin-related protein 1,immunotherapy,mitochondrial dynamics,t cell exhaustion,tumor microenvironment

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