Tissue-resident FOLR2+ macrophages associate with tumor-infiltrating CD8+ T cells and with increased survival of breast cancer patients. Tissue-resident FOLR2+ macrophages associate with tumor-infiltrating CD8+ T cells and with increased survival of breast cancer patients
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Macrophage infiltration is a hallmark of solid cancers and overall macrophage infiltration correlates with lower patient survival and resistance to therapy. Tumor- associated macrophages, however, are phenotypically and functionally heterogeneous. Specific subsets of tumor-associated macrophage might be endowed with antagonistic roles on cancer progression and on the development of anti-tumor immunity. Here, we identify a discrete population of FOLR2 + tissue-resident macrophages in healthy mammary gland and breast cancer primary tumors. FOLR2 + macrophages localize in perivascular areas in the tumor stroma, where they interact with CD8 + T cells. Moreover, FOLR2 + macrophages efficiently prime effector CD8 + T cells ex vivo . The density of FOLR2 + macrophages in tumors positively correlates with better patient survival. This study highlights antagonistic roles for tumor-associated macrophage subsets and paves the way for subset-specific therapeutic interventions in macrophages-based cancer therapies. Overall design: Tumor infiltrating myeloid cells were isolated from human and murine breast tumors for single cell RNA-seq or bulk RNA-seq analysis
巨噬细胞浸润是实体瘤的标志性特征，整体巨噬细胞浸润水平与患者生存期缩短及治疗抵抗呈显著相关。然而，肿瘤相关巨噬细胞（tumor-associated macrophages）在表型与功能层面均具有异质性。特定的肿瘤相关巨噬细胞亚群，或许在癌症进展与抗肿瘤免疫的建立过程中发挥拮抗性功能。本研究在健康乳腺组织与原发性乳腺癌组织中，鉴定出一类离散的FOLR2+组织驻留巨噬细胞群。FOLR2+巨噬细胞定位于肿瘤间质的血管周围区域，并在此与CD8+ T细胞发生相互作用。此外，FOLR2+巨噬细胞在体外可有效致敏效应性CD8+ T细胞。肿瘤内FOLR2+巨噬细胞的密度与患者更佳的生存期呈正相关。本研究揭示了肿瘤相关巨噬细胞亚群的拮抗性功能，并为基于巨噬细胞的癌症治疗中针对特定亚群的干预策略铺平了道路。整体实验设计：从人类及小鼠乳腺癌组织中分离肿瘤浸润髓系细胞，用于单细胞RNA测序（single cell RNA-seq）或批量RNA测序（bulk RNA-seq）分析。
