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- W4365512076 abstract "Abstract Adipose tissue in the mammary gland undergoes dramatic remodeling during obesity and is involved in numerous metabolic diseases. However, how obesity-driven remodeling in adipose tissue regulates anti-tumor immunity remains unclear. Here we provide the detailed cellular atlases of mouse mammary fat pad and tumor at single-cell resolution in lean and obese mice. By leveraging scRNA-seq, we found that high-fat feeding causes a marked increase of macrophage in adipose tissue. Interestingly, a subset of macrophages expressing high levels of C1q complex genes is accumulated in obese subjects. We found that glucocorticoid may as a key regulator of C1q+ macrophage identity. Synthetic glucocorticoid, Dexamethasone, triggers C1q expression in macrophages. We found that C1q+ macrophage derived C1q complex could suppress CD8+ T cell response, thus fueling breast cancer progression. In mouse TNBC tumor, we uncovered a specific inflammatory responsive tumor subset in obese tumors with high CCR2 ligand expression. Obesity-induced TNFα exposure triggers of breast cancer cells reprogramming and CCR2 ligand production. Consequently, CCR2 ligands promote macrophage into tumor. Moreover, depletion of macrophages by anti-CSF1R suppresses tumor growth in obese mice. Our findings define a novel fundamental mechanism of C1q+ macrophage involved in anti-tumor response in obesity. Citation Format: Tao Zhang, Shimeng Liu, Myles Brown. Obesity-trained C1q+ macrophages compromiseT cell anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB202." @default.
- W4365512076 created "2023-04-15" @default.
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- W4365512076 date "2023-04-14" @default.
- W4365512076 modified "2023-10-17" @default.
- W4365512076 title "Abstract LB202: Obesity-trained C1q+ macrophages compromiseT cell anti-tumor immunity" @default.
- W4365512076 doi "https://doi.org/10.1158/1538-7445.am2023-lb202" @default.
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