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

SUMMARY Macrophage infiltration is a hallmark of solid cancers and overall macrophage infiltration is correlated with lower patient survival and resistance to therapy. However, tumor-associated macrophages are phenotypically and functionally heterogeneous. Specific tumor-associated macrophage subsets might be endowed with antagonistic role on cancer progression and on the development of anti-tumor immunity. For instance, monocyte-derived TREM2 + tumor-associated macrophages have pro-tumorigenic and immunosuppressive functions. Here, we identify a discrete population of FOLR2 + tumor-associated macrophages positively correlating with patient survival in breast cancer. FOLR2 + macrophages are evolutionarily conserved across species and populate human and murine healthy mammary gland. Moreover, FOLR2 + macrophages co-localize with lymphoid aggregates containing CD8 + T cells in breast cancer and across ten other types of cancers. This study highlights antagonistic roles for tumor-associated macrophage subsets and paves the way for subset-specific therapeutic interventions in macrophages-based cancer therapies.