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Abstract Obesity markedly impacts the onset and progression of various tumors. Yet, the mechanisms by which obesity-driven remodeling in macrophages modulates tumor progression are not yet fully elucidated. Using single-cell RNA sequencing and in vivo syngeneic murine models, we identified an enriched subset of macrophages expressing high levels of C1q complex genes in the adipose tissue of obese mice. Intriguingly, these C1q-positive macrophages are also prevalent within the tumor microenvironment. Our data suggest that obesity induces cell apoptosis in both adipocytes and tumor cells, and that macrophages engulf these apoptotic cells via a C1q-dependent pathway, thus promoting immunosuppression. Moreover, C1q deficiency in mice impairs tumor growth. Notably, C1q is upregulated in human breast cancer and is associated with poor prognosis. Our results suggest that targeting C1q could be an effective method for breast cancer treatment. Citation Format: Tao Zhang, Shimeng Liu, Myles Brown. Obesity promotes breast cancer progression via complement 1q abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 7461.
Zhang et al. (2024) studied this question.