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Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment

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资源类型：
Pubmed体系：
作者：
Zhou Wenhao[1,2,3] ; Kawashima Shusuke[4,5] ; Ishino Takamasa[1,5,6] ; Kawase Katsushige[5,7] ; Ueda Youki[1] ; Yamashita Kazuo[8] ; Watanabe Tomofumi[1,9] ; Kawazu Masahito[5] ; Dansako Hiromichi[1] ; Suzuki Yutaka[10] ; Nishikawa Hiroyoshi[2,11] ; Inozume Takashi[2,5] ; Nagasaki Joji[1,5] ; Togashi Yosuke[1,5,11] ;
机构： [1]Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan [2]Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan [3]Department of Urology Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China [4]Department of Dermatology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan [5]Chiba Cancer Center, Research Institute, Division of Cell Therapy, Chiba 260-8717, Japan [6]Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan [7]Department of Otorhinolaryngology/Head & Neck Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan [8]KOTAI Biotechnologies, Inc. Osaka 565-0871, Japan [9]Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-0932, Japan [10]Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Kashiwa 277-8568, Japan [11]Division of Cancer Immunology, National Cancer Center, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), Tokyo 104-0045, Kashiwa 277-8577, Japan
出处：
DOI： 10.1016/j.celrep.2024.113797

摘要：
Immune checkpoint inhibitors exert clinical efficacy against various types of cancer through reinvigoration of exhausted CD8+ T cells that attack cancer cells directly in the tumor microenvironment (TME). Using single-cell sequencing and mouse models, we show that CXCL13, highly expressed in tumor-infiltrating exhausted CD8+ T cells, induces CD4+ follicular helper T (TFH) cell infiltration, contributing to anti-tumor immunity. Furthermore, a part of the TFH cells in the TME exhibits cytotoxicity and directly attacks major histocompatibility complex-II-expressing tumors. TFH-like cytotoxic CD4+ T cells have high LAG-3/BLIMP1 and low TCF1 expression without self-renewal ability, whereas non-cytotoxic TFH cells express low LAG-3/BLIMP1 and high TCF1 with self-renewal ability, closely resembling the relationship between terminally differentiated and stem-like progenitor exhaustion in CD8+ T cells, respectively. Our findings provide deep insights into TFH-like CD4+ T cell exhaustion with helper progenitor and cytotoxic differentiated functions, mediating anti-tumor immunity orchestrally with CD8+ T cells.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

基金：
This study was supported by Grants-in-Aid for Scientific Research (Challenging Exploratory Research no. 22K1945904 to Y.T., S grant no. 21H05051 to Y.T., B grant no. 20H03694 to Y.T., C grant no. 19K08744 to T. Inozume., Research Activity Start-up no. 22K20824 to J.N., Early-Career Scientists no. 22K15472 to Y.U., and no. 23K14594 to J.N.) from Japan Society for the Promotion of Science (JSPS); the Project for Cancer Research and Therapeutic Evolution (P-CREATE, no. 19cm0106502 to M.K. and no. 21cm0106383 to K.Y. and Y.T.); the Practical Research for Innovative Cancer Control (no. 19ck0106521h0001 to K.Y. and Y.T. and no. 22ck0106775h0001 to J.N.); the Core Research for Evolutional Science and Technology (CREST, no. 22gm1810002s0101 to Y.T.) from the Japan Agency for Medical Research and Development (AMED); the Fusion Oriented Research for disruptive Science and Technology (FOREST) (no. 21- 211033868 to Y.T.) from Japan Science and Technology Agency (JST); the Naito Foundation (to J.N. and Y.T.); the Astellas Foundation for Research on Metabolic Disorders (to Y.T.); the Wesco Foundation (to Y.T.); the Uehara Memorial Foundation (to J.N. and Y.T.); the Senri Life Science Foundation (to Y.T.); the Relay for Life Japan Cancer Society Foundation (to Y.T.); the Japan Research Foundation for Clinical Pharmacology (to Y.T.); the Takeda Science Foundation (to J.N.); the Kowa Life Science Foundation (to J.N.); the Chugai Foundation for Innovative Drug Discovery Science (to J.N.); the Yasuda Medical Foundation (to J.N.); and the SGH Foundation (to J.N.). This study was partially supported by KOTAI Biotechnologies, Inc.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
最新[2023]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
第一作者：
第一作者机构： [1]Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan [2]Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan [3]Department of Urology Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan [5]Chiba Cancer Center, Research Institute, Division of Cell Therapy, Chiba 260-8717, Japan [11]Division of Cancer Immunology, National Cancer Center, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), Tokyo 104-0045, Kashiwa 277-8577, Japan
推荐引用方式(GB/T 7714)：
Zhou Wenhao,Kawashima Shusuke,Ishino Takamasa,et al.Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment[J].Cell Reports.2024,43(2):113797.doi:10.1016/j.celrep.2024.113797.
APA：
Zhou Wenhao,Kawashima Shusuke,Ishino Takamasa,Kawase Katsushige,Ueda Youki...&Togashi Yosuke.(2024).Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment.Cell Reports,43,(2)
MLA：
Zhou Wenhao,et al."Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment".Cell Reports 43..2(2024):113797

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