ID | 66974 |
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Kawasaki, Kento
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Noma, Kazuhiro
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Kato, Takuya
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ohara, Toshiaki
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Tanabe, Shunsuke
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Takeda, Yasushige
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Matsumoto, Hijiri
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nishimura, Seitaro
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kunitomo, Tomoyoshi
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Akai, Masaaki
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kobayashi, Teruki
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nishiwaki, Noriyuki
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kashima, Hajime
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Maeda, Naoaki
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kikuchi, Satoru
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Tazawa, Hiroshi
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Shirakawa, Yasuhiro
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Fujiwara, Toshiyoshi
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Abstract | The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.
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Keywords | Esophageal cancer
Cancer-associated fibroblasts
Programmed cell death 1
Program cell death ligand 1
Immune checkpoint inhibitors
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Note | The version of record of this article, first published in Cancer Immunology, Immunotherapy, is available online at Publisher’s website: http://dx.doi.org/10.1007/s00262-023-03531-2
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Published Date | 2023-09-05
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Publication Title |
Cancer Immunology, Immunotherapy
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Volume | volume72
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Issue | issue11
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Publisher | Springer Science and Business Media LLC
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Start Page | 3787
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End Page | 3802
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ISSN | 0340-7004
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NCID | AA00598499
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © The Author(s) 2023
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File Version | publisher
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Related Url | isVersionOf https://doi.org/10.1007/s00262-023-03531-2
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License | http://creativecommons.org/licenses/by/4.0/
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Citation | Kawasaki, K., Noma, K., Kato, T. et al. PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer. Cancer Immunol Immunother 72, 3787–3802 (2023). https://doi.org/10.1007/s00262-023-03531-2
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Funder Name |
Okayama University
Japan Society for the Promotion of Science
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助成番号 | JP21K08754
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