Unveiling the key mechanisms of FOLR2+ macrophage-mediated antitumor immunity in breast cancer using integrated single-cell RNA sequencing and bulk RNA sequencing

利用整合的单细胞 RNA 测序和批量 RNA 测序揭示乳腺癌中 FOLR2+ 巨噬细胞介导的抗肿瘤免疫的关键机制

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作者:Sixuan Wu #, Baohong Jiang #, Zhimin Li #, Yuanbin Tang, Lunqi Luo, Wenjie Feng, Yiling Jiang, Yeru Tan, Yuehua Li

Abstract

Breast cancer (BRCA) is a common malignant tumor, and its immune microenvironment plays a crucial role in disease progression. In this research, we utilized single-cell RNA sequencing and bulk RNA sequencing technologies, combined with in vivo and in vitro experiments, to thoroughly investigate the immunological functions and mechanisms of FOLR2+ macrophages in BRCA. Our findings demonstrate a significant enhancement in the interaction between FOLR2+ macrophages and CD8+ T cells within the tumor tissues of BRCA patients. FOLR2 is closely associated with T cell infiltration in the tumor microenvironment of BRCA patients, particularly with CD8+ T cells. By secreting CXCL9 and engaging with CXCR3, FOLR2+ macrophages can activate the functionality of CD8+ T cells, thereby promoting cancer cell apoptosis. Further animal experiments confirm that FOLR2+ macrophages activate CD8+ T cells through the CXCL9-CXCR3 axis, exhibiting an antitumor immunity effect in BRCA. FOLR2+ macrophages play a crucial role in antitumor immunity in BRCA through the CXCL9-CXCR3 axis.

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