Tissue-resident FOLR2+ macrophages associate with tumor-infiltrating CD8+ T cells and with increased survival of breast cancer patients

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