Regulatory B cells drive immune evasion in the tumor microenvironment and are involved peritoneal metastasis in gastric cancer
Abstract Peritoneal metastasis (PM) of gastric cancer (GC) has an immune escape environment. Regulatory B cells (Bregs), characterized by IL-10 production, play an important role in the tumor immunity; however, the function of Bregs in PM remains unclear. We investigated the frequency and effects of...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-11887-x |
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| author | Yuta Fujiwara Jun Kinoshita Mari Shimada Hiroto Saito Toshikatsu Tsuji Daisuke Yamamoto Hideki Moriyama Motoki Horii Sachiyo Nomura Takashi Matsushita Yasuhiko Yamamoto Noriyuki Inaki |
| author_facet | Yuta Fujiwara Jun Kinoshita Mari Shimada Hiroto Saito Toshikatsu Tsuji Daisuke Yamamoto Hideki Moriyama Motoki Horii Sachiyo Nomura Takashi Matsushita Yasuhiko Yamamoto Noriyuki Inaki |
| author_sort | Yuta Fujiwara |
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| description | Abstract Peritoneal metastasis (PM) of gastric cancer (GC) has an immune escape environment. Regulatory B cells (Bregs), characterized by IL-10 production, play an important role in the tumor immunity; however, the function of Bregs in PM remains unclear. We investigated the frequency and effects of Bregs on other immune cells in the PM using clinical specimens and mouse models of PM. In the peripheral blood and ascites, Breg frequency was significantly higher in patients with GC with PM than in those without PM. In clinical PM samples, Breg frequency was an independent prognostic factor. In the mouse PM model, peritoneal tumors showed higher Breg infiltration than subcutaneous tumors. In the PTEN-deficient PM model, activation of Bregs promoted ascites and peritoneal tumor growth, decreased the infiltration of CD8+ T cells, and increased the infiltration of M2 macrophages. In contrast, treatment with wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, suppressed Breg infiltration, resulting in decreased M2 macrophage infiltration and increased CD8+ T cell infiltration. Bregs are indicated to be involved in immunosuppression of PM and are promising targets for improving the efficacy of immunotherapy against PM. |
| format | Article |
| id | doaj-art-3cbd76e2dee54b41ba7bd50af94730ca |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-3cbd76e2dee54b41ba7bd50af94730ca2025-08-20T04:02:46ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-11887-xRegulatory B cells drive immune evasion in the tumor microenvironment and are involved peritoneal metastasis in gastric cancerYuta Fujiwara0Jun Kinoshita1Mari Shimada2Hiroto Saito3Toshikatsu Tsuji4Daisuke Yamamoto5Hideki Moriyama6Motoki Horii7Sachiyo Nomura8Takashi Matsushita9Yasuhiko Yamamoto10Noriyuki Inaki11Department of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa UniversityDepartment of Dermatology, Kanazawa University Graduate School of Medical SciencesDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of TokyoDepartment of Dermatology, Kanazawa University Graduate School of Medical SciencesDepartment of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical SciencesDepartment of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa UniversityAbstract Peritoneal metastasis (PM) of gastric cancer (GC) has an immune escape environment. Regulatory B cells (Bregs), characterized by IL-10 production, play an important role in the tumor immunity; however, the function of Bregs in PM remains unclear. We investigated the frequency and effects of Bregs on other immune cells in the PM using clinical specimens and mouse models of PM. In the peripheral blood and ascites, Breg frequency was significantly higher in patients with GC with PM than in those without PM. In clinical PM samples, Breg frequency was an independent prognostic factor. In the mouse PM model, peritoneal tumors showed higher Breg infiltration than subcutaneous tumors. In the PTEN-deficient PM model, activation of Bregs promoted ascites and peritoneal tumor growth, decreased the infiltration of CD8+ T cells, and increased the infiltration of M2 macrophages. In contrast, treatment with wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, suppressed Breg infiltration, resulting in decreased M2 macrophage infiltration and increased CD8+ T cell infiltration. Bregs are indicated to be involved in immunosuppression of PM and are promising targets for improving the efficacy of immunotherapy against PM.https://doi.org/10.1038/s41598-025-11887-xRegulatory B cellGastric cancerPeritoneal metastasisPI3K/AktWortmannin |
| spellingShingle | Yuta Fujiwara Jun Kinoshita Mari Shimada Hiroto Saito Toshikatsu Tsuji Daisuke Yamamoto Hideki Moriyama Motoki Horii Sachiyo Nomura Takashi Matsushita Yasuhiko Yamamoto Noriyuki Inaki Regulatory B cells drive immune evasion in the tumor microenvironment and are involved peritoneal metastasis in gastric cancer Scientific Reports Regulatory B cell Gastric cancer Peritoneal metastasis PI3K/Akt Wortmannin |
| title | Regulatory B cells drive immune evasion in the tumor microenvironment and are involved peritoneal metastasis in gastric cancer |
| title_full | Regulatory B cells drive immune evasion in the tumor microenvironment and are involved peritoneal metastasis in gastric cancer |
| title_fullStr | Regulatory B cells drive immune evasion in the tumor microenvironment and are involved peritoneal metastasis in gastric cancer |
| title_full_unstemmed | Regulatory B cells drive immune evasion in the tumor microenvironment and are involved peritoneal metastasis in gastric cancer |
| title_short | Regulatory B cells drive immune evasion in the tumor microenvironment and are involved peritoneal metastasis in gastric cancer |
| title_sort | regulatory b cells drive immune evasion in the tumor microenvironment and are involved peritoneal metastasis in gastric cancer |
| topic | Regulatory B cell Gastric cancer Peritoneal metastasis PI3K/Akt Wortmannin |
| url | https://doi.org/10.1038/s41598-025-11887-x |
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