Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer
Abstract Patients with peritoneal metastasized colorectal cancer (PM-CRC) have a dismal prognosis. We hypothesized that an immunosuppressive environment in the peritoneal cavity underlies poor prognosis. We define the composition of the human peritoneal immune system (PerIS) using single-cell techno...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58999-6 |
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| author | J. Saris A. Y. F. Li Yim S. Bootsma K. J. Lenos R. Franco Fernandez H. N. Khan J. Verhoeff D. Poel N. M. Mrzlikar L. Xiong M. P. Schijven N. C. T. van Grieken O. Kranenburg M. E. Wildenberg A. Logiantara C. Jongerius J. J. Garcia Vallejo S. S. Gisbertz S. Derks J. B. Tuynman G. R. A. M. D’Haens L. Vermeulen J. Grootjans |
| author_facet | J. Saris A. Y. F. Li Yim S. Bootsma K. J. Lenos R. Franco Fernandez H. N. Khan J. Verhoeff D. Poel N. M. Mrzlikar L. Xiong M. P. Schijven N. C. T. van Grieken O. Kranenburg M. E. Wildenberg A. Logiantara C. Jongerius J. J. Garcia Vallejo S. S. Gisbertz S. Derks J. B. Tuynman G. R. A. M. D’Haens L. Vermeulen J. Grootjans |
| author_sort | J. Saris |
| collection | DOAJ |
| description | Abstract Patients with peritoneal metastasized colorectal cancer (PM-CRC) have a dismal prognosis. We hypothesized that an immunosuppressive environment in the peritoneal cavity underlies poor prognosis. We define the composition of the human peritoneal immune system (PerIS) using single-cell technologies in 18 patients with- and without PM-CRC, as well as in matched peritoneal metastases (n = 8). Here we show that the PerIS contains abundant immunosuppressive C1Q + VSIG4 + and SPP1 + VSIG4 + peritoneal-resident macrophages (PRMs), as well as monocyte-like cavity macrophages (mono-CMs), which share features with tumor-associated macrophages, even in homeostasis. In PM-CRC, expression of immunosuppressive cytokines IL10 and VEGF increases, while simultaneously expression of antigen-presenting molecules decreases in PRMs. These intratumoral suppressive PRMs originate from the PerIS, and intraperitoneal depletion of PRMs in vivo using anti-CSF1R combined with anti-PD1 significantly reduces tumor burden and improves survival. Thus, PRMs define a metastatic site-specific immunosuppressive niche, and targeting PRMs is a promising treatment strategy for PM-CRC. |
| format | Article |
| id | doaj-art-b30c0cce5a804308abc2fc917e205bc3 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b30c0cce5a804308abc2fc917e205bc32025-08-20T02:55:35ZengNature PortfolioNature Communications2041-17232025-04-0116111710.1038/s41467-025-58999-6Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancerJ. Saris0A. Y. F. Li Yim1S. Bootsma2K. J. Lenos3R. Franco Fernandez4H. N. Khan5J. Verhoeff6D. Poel7N. M. Mrzlikar8L. Xiong9M. P. Schijven10N. C. T. van Grieken11O. Kranenburg12M. E. Wildenberg13A. Logiantara14C. Jongerius15J. J. Garcia Vallejo16S. S. Gisbertz17S. Derks18J. B. Tuynman19G. R. A. M. D’Haens20L. Vermeulen21J. Grootjans22Department of Gastroenterology and Hepatology, Amsterdam UMC, University of AmsterdamDepartment of Gastroenterology and Hepatology, Amsterdam UMC, University of AmsterdamAmsterdam Gastroenterology Endocrinology MetabolismAmsterdam Gastroenterology Endocrinology MetabolismAmsterdam Gastroenterology Endocrinology MetabolismAmsterdam Gastroenterology Endocrinology MetabolismAmsterdam Gastroenterology Endocrinology MetabolismAmsterdam Gastroenterology Endocrinology MetabolismAmsterdam Gastroenterology Endocrinology MetabolismTytgat Institute for Liver and Intestinal Research, Amsterdam UMC, University of AmsterdamAmsterdam Gastroenterology Endocrinology MetabolismCancer Center AmsterdamLaboratory Translational Oncology, Division of Imaging and Cancer, University Medical Center UtrechtDepartment of Gastroenterology and Hepatology, Amsterdam UMC, University of AmsterdamLaboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam UMC, University of AmsterdamAmsterdam Gastroenterology Endocrinology MetabolismCancer Center AmsterdamCancer Center AmsterdamCancer Center AmsterdamCancer Center AmsterdamDepartment of Gastroenterology and Hepatology, Amsterdam UMC, University of AmsterdamAmsterdam Gastroenterology Endocrinology MetabolismDepartment of Gastroenterology and Hepatology, Amsterdam UMC, University of AmsterdamAbstract Patients with peritoneal metastasized colorectal cancer (PM-CRC) have a dismal prognosis. We hypothesized that an immunosuppressive environment in the peritoneal cavity underlies poor prognosis. We define the composition of the human peritoneal immune system (PerIS) using single-cell technologies in 18 patients with- and without PM-CRC, as well as in matched peritoneal metastases (n = 8). Here we show that the PerIS contains abundant immunosuppressive C1Q + VSIG4 + and SPP1 + VSIG4 + peritoneal-resident macrophages (PRMs), as well as monocyte-like cavity macrophages (mono-CMs), which share features with tumor-associated macrophages, even in homeostasis. In PM-CRC, expression of immunosuppressive cytokines IL10 and VEGF increases, while simultaneously expression of antigen-presenting molecules decreases in PRMs. These intratumoral suppressive PRMs originate from the PerIS, and intraperitoneal depletion of PRMs in vivo using anti-CSF1R combined with anti-PD1 significantly reduces tumor burden and improves survival. Thus, PRMs define a metastatic site-specific immunosuppressive niche, and targeting PRMs is a promising treatment strategy for PM-CRC.https://doi.org/10.1038/s41467-025-58999-6 |
| spellingShingle | J. Saris A. Y. F. Li Yim S. Bootsma K. J. Lenos R. Franco Fernandez H. N. Khan J. Verhoeff D. Poel N. M. Mrzlikar L. Xiong M. P. Schijven N. C. T. van Grieken O. Kranenburg M. E. Wildenberg A. Logiantara C. Jongerius J. J. Garcia Vallejo S. S. Gisbertz S. Derks J. B. Tuynman G. R. A. M. D’Haens L. Vermeulen J. Grootjans Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer Nature Communications |
| title | Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer |
| title_full | Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer |
| title_fullStr | Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer |
| title_full_unstemmed | Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer |
| title_short | Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer |
| title_sort | peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer |
| url | https://doi.org/10.1038/s41467-025-58999-6 |
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