What question did this study set out to answer?

This research aims to understand the roles of metastasis associated macrophages in gastric cancer peritoneal metastasis, focusing on their effects on tumor growth and immune response.

April 5, 2026

Abstract 1584: Metastasis associated macrophages drive immunosuppression and fibrosis in gastric peritoneal carcinomatosis

Key Points

This research aims to understand the roles of metastasis associated macrophages in gastric cancer peritoneal metastasis, focusing on their effects on tumor growth and immune response.
Conducted transcriptomic analysis of malignant ascites and peritoneal tumor samples.
Used syngeneic murine models to assess the impact of targeted macrophage depletion on tumor growth.
Performed bulk RNA sequencing to evaluate gene expression changes post macrophage depletion.
Measured cytokine levels using multiplex cytokine arrays.
Conducted co-culture assays of isolated macrophages and T cells to study immune response.
Targeted macrophage depletion resulted in an 80% reduction in tumor weights and overall tumor volume.
Depletion of macrophages led to increased T cell activation and reduced expression of pro-fibrotic genes.
Significant inhibition of the immunosuppressive cytokines IL-10, IL-6, and CXCL1 was observed.
Metastasis associated macrophages inhibited T cell activation in co-culture experiments.

Abstract

Abstract Gastric cancer peritoneal metastasis (GC-PM) remains a lethal disease with 5-6% overall survival. Macrophages are the predominant antigen presenting cells in the peritoneum initiating innate and adaptive responses. Thus, macrophage-based therapies may be an important avenue for immune based therapeutic strategies. However, the role and regulators of metastasis associated macrophages (MAMs) in GC-PM remain uncertain. Comparative transcriptomic analysis of malignant ascites and solid peritoneal tumor implants demonstrated that MAMs are a predominant cell type in the tumor microenvironment. Using syngeneic murine models of gastric carcinomatosis, we observed that targeted macrophage depletion restricted tumor growth as evidenced by 80% reduction in tumor weights, total body tumor volume, number of nodules, and malignant bowel obstruction. Bulk RNA sequencing of the malignant ascites demonstrated upregulation of pathways associated with T cell activation, differentiation and proliferation with macrophage depletion. In addition, bulk RNA sequencing of the macrophage-depleted tumor tissue showed downregulation of pro-fibrotic genes Col1a1, Fgf2 and Itgb1 compared with controls. Multiplex cytokine array revealed inhibition of immunosuppressive chemokines IL-10, IL-6 and CXCL1 with macrophage depletion. Functionally, co-cultured isolated MAMs isolated from malignant ascites and tumor nodules inhibited naïve polyclonal CD4+ T cell activation ex-vivo. Taken together, we elucidate dual mechanisms by which metastasis associated macrophages promote oncogenesis through altering adaptive anti-tumor immunity and promoting fibrosis in gastric peritoneal metastasis. Future studies will identify macrophage subsets that can be targeted for potential therapies. Citation Format: Lilia Turcios, Neelima Hosamani, Ellen Beswick, Maria Carey, Joseph Kim, Mautin Barry-Hundeyin. Metastasis associated macrophages drive immunosuppression and fibrosis in gastric peritoneal carcinomatosis abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1584.

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Cite This Study

Turcios et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fceba79560c99a0a2a4c https://doi.org/https://doi.org/10.1158/1538-7445.am2026-1584

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