Tissue-resident FOLR2+ macrophages associate with CD8+ T cell infiltration in human breast cancer

Abstract

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 distinct roles on cancer progression and antitumor 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. 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 specific roles for tumor-associated macrophage subsets and paves the way for subset-targeted therapeutic interventions in macrophages-based cancer therapies.

Keywords: CD8(+) T lymphocytes; FOLR2; TREM2; breast cancer; single-cell RNA sequencing; tissue-resident macrophages.