Abstract B019: Regulatory macrophages contribute to tumor cell plasticity in colorectal cancer metastases

Abstract

Abstract Metastatic disease is the common cause of death in colorectal cancer. To better understand the cellular landscape of colorectal metastasis, we profiled primary tumors and liver, lung, and peritoneal metastases using single-cell RNA sequencing. Our analysis revealed a subset of tumor epithelial cells with a highly plastic transcription profile and, inversely, low expression of stemness markers. Tumor cells with plasticity markers were spatially enriched at the tumor- stroma interface with exposure to tissue microenvironmental factors. Cell-free malignant ascites, which recapitulates the tumor microenvironment, impaired expression of proliferation and stem- like markers in favor of plasticity markers and enhanced migration of tumor cells. Furthermore, Co-culture of colorectal tumor cells with CD11b+ macrophages isolated from malignant ascites from patients was sufficient to recapitulate tumor cell plasticity. Profiling of tumor-associated macrophages identified enrichment for a lipid-handling features and high spatial correlation with plastic tumor cells. Taken together, we demonstrate that tumor-associated macrophages contribute to disease progression through development of pro-malignant features. Citation Format: Matthew A. Cottam, Muhammad B. Mirza, Emily N. Arner, Marium Siddiqui, Clare Lipscombe, Zaid Hatem, Katy E. Beckermann, Kamran Idrees. Regulatory macrophages contribute to tumor cell plasticity in colorectal cancer metastases [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B019.