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

Cell. 2022 Mar 31;185(7):1189-1207.e25. doi: 10.1016/j.cell.2022.02.021. Epub 2022 Mar 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast / immunology
  • Breast Neoplasms* / epidemiology
  • Breast Neoplasms* / immunology
  • CD8-Positive T-Lymphocytes
  • Female
  • Folate Receptor 2
  • Humans
  • Lymphocytes, Tumor-Infiltrating
  • Macrophages*
  • Prognosis


  • FOLR2 protein, human
  • Folate Receptor 2