CXCR3+ monocytes as regulators of tumor immunity in triple-negative breast cancer 4462

Abstract Description Monocytes are critical modulators of cancer progression, with CXCR3+ monocytes linked to enhanced responses to immunotherapies. We investigated the heterogeneity and function of CXCR3+ monocytes in two triple-negative breast cancer (TNBC) mouse models (AT-3 and EO771). AT-3 tumors exhibit slower growth but greater metastatic potential compared to EO771, reflecting distinct progression dynamics. CyTOF mass cytometry profiling of tumor-infiltrating myeloid cells identified subsets of CXCR3+ myeloid cells, including CXCR3+ F4/80 macrophages and CXCR3+ Ly6C+ monocytes, which were enriched in EO771 tumors. Additionally, CXCR3+ monocyte progenitors were found in the bone marrow of EO771-bearing mice, suggesting a hematopoietic origin. To assess CXCR3+ monocyte function, we performed RNA sequencing on monocytes from wild-type and CXCR3KO mice, revealing significant transcriptional changes, including altered IL-10 signaling. Using a CXCR3fl/fl/CX3CR1cre model, targeted CXCR3 deletion in monocytes resulted in increased tumor growth, highlighting their role in tumor suppression. These findings demonstrate the importance of CXCR3+ monocytes in anti-tumor immunity and lay the groundwork for future studies to uncover their impact on T cell-mediated responses and immunotherapy outcomes. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)