Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment
Summary: 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 i...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724001256 |
| _version_ | 1797291784226734080 |
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| author | Wenhao Zhou Shusuke Kawashima Takamasa Ishino Katsushige Kawase Youki Ueda Kazuo Yamashita Tomofumi Watanabe Masahito Kawazu Hiromichi Dansako Yutaka Suzuki Hiroyoshi Nishikawa Takashi Inozume Joji Nagasaki Yosuke Togashi |
| author_facet | Wenhao Zhou Shusuke Kawashima Takamasa Ishino Katsushige Kawase Youki Ueda Kazuo Yamashita Tomofumi Watanabe Masahito Kawazu Hiromichi Dansako Yutaka Suzuki Hiroyoshi Nishikawa Takashi Inozume Joji Nagasaki Yosuke Togashi |
| author_sort | Wenhao Zhou |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-07T19:42:45Z |
| format | Article |
| id | doaj.art-a16afc6c6d2a44839375efb4ad0cb6e6 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-07T19:42:45Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a16afc6c6d2a44839375efb4ad0cb6e62024-02-29T05:19:00ZengElsevierCell Reports2211-12472024-02-01432113797Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironmentWenhao Zhou0Shusuke Kawashima1Takamasa Ishino2Katsushige Kawase3Youki Ueda4Kazuo Yamashita5Tomofumi Watanabe6Masahito Kawazu7Hiromichi Dansako8Yutaka Suzuki9Hiroyoshi Nishikawa10Takashi Inozume11Joji Nagasaki12Yosuke Togashi13Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Urology Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, ChinaDepartment of Dermatology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; Chiba Cancer Center, Research Institute, Division of Cell Therapy, Chiba 260-8717, JapanDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; Chiba Cancer Center, Research Institute, Division of Cell Therapy, Chiba 260-8717, Japan; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba 260-8670, JapanChiba Cancer Center, Research Institute, Division of Cell Therapy, Chiba 260-8717, Japan; Department of Otorhinolaryngology/Head & Neck Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, JapanDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanKOTAI Biotechnologies, Inc. Osaka 565-0871, JapanDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-0932, JapanChiba Cancer Center, Research Institute, Division of Cell Therapy, Chiba 260-8717, JapanDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Kashiwa 277-8568, JapanDepartment of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Division of Cancer Immunology, National Cancer Center, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), Tokyo 104-0045, Kashiwa 277-8577, JapanDepartment of Dermatology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; Chiba Cancer Center, Research Institute, Division of Cell Therapy, Chiba 260-8717, JapanDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; Chiba Cancer Center, Research Institute, Division of Cell Therapy, Chiba 260-8717, Japan; Corresponding authorDepartment of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; Chiba Cancer Center, Research Institute, Division of Cell Therapy, Chiba 260-8717, Japan; Division of Cancer Immunology, National Cancer Center, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), Tokyo 104-0045, Kashiwa 277-8577, Japan; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724001256CP: Cancer |
| spellingShingle | Wenhao Zhou Shusuke Kawashima Takamasa Ishino Katsushige Kawase Youki Ueda Kazuo Yamashita Tomofumi Watanabe Masahito Kawazu Hiromichi Dansako Yutaka Suzuki Hiroyoshi Nishikawa Takashi Inozume Joji Nagasaki Yosuke Togashi Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment Cell Reports CP: Cancer |
| title | Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment |
| title_full | Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment |
| title_fullStr | Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment |
| title_full_unstemmed | Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment |
| title_short | Stem-like progenitor and terminally differentiated TFH-like CD4+ T cell exhaustion in the tumor microenvironment |
| title_sort | stem like progenitor and terminally differentiated tfh like cd4 t cell exhaustion in the tumor microenvironment |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724001256 |
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