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Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer

  • 0Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Nature Communications +

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April 17, 2025

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April 17, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Peritoneal-resident macrophages (PRMs) create an immunosuppressive environment in patients with colorectal cancer metastasis. Targeting these PRMs offers a promising new treatment strategy for peritoneal metastasis.

Area Of Science

  • Immunology
  • Oncology
  • Cell Biology

Background

  • Peritoneal metastasis from colorectal cancer (PM-CRC) is associated with a poor prognosis.
  • An immunosuppressive peritoneal microenvironment is hypothesized to contribute to this dismal outcome.

Purpose Of The Study

  • To define the composition of the human peritoneal immune system (PerIS) in patients with and without PM-CRC.
  • To investigate the role of peritoneal-resident macrophages (PRMs) in the immunosuppressive environment of PM-CRC.

Main Methods

  • Single-cell technologies were employed to analyze the PerIS in 18 patients with and without PM-CRC, and matched peritoneal metastases (n=8).
  • Immunohistochemistry and flow cytometry were used to characterize macrophage populations and cytokine expression.

Main Results

  • The PerIS contains abundant immunosuppressive C1Q+VSIG4+ and SPP1+VSIG4+ PRMs and monocyte-like cavity macrophages (mono-CMs).
  • In PM-CRC, PRMs exhibit increased immunosuppressive cytokines (IL10, VEGF) and decreased antigen-presenting molecules.
  • Intraperitoneal depletion of PRMs using anti-CSF1R and anti-PD1 reduced tumor burden and improved survival in vivo.

Conclusions

  • PRMs establish a metastatic site-specific immunosuppressive niche in PM-CRC.
  • Targeting PRMs represents a promising therapeutic strategy for PM-CRC.