4.8 Article

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

Journal

CELL
Volume 185, Issue 7, Pages 1189-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2022.02.021

Keywords

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Funding

  1. SiRIC-Curie Program [INCa-DGOS-12554]
  2. Labex DCBIOL [ANR-10-IDEX-0001-02 PSL, ANR-11-LABX-0043]
  3. Fondation ARC [PA20181207706]
  4. Ligue Nationale contre le cancer [RS19/75-92]
  5. Center of Clinical Investigation (CIC IGR-Curie) [1428]
  6. ITMO-CancerAviesan (Plan Cancer III) [ANR-10-EQPX-03, ANR-10-INBS-09-08]
  7. SiRIC-Curie program (SiRIC Grant) [INCa-DGOS-4654]
  8. NIHR Manchester BRC
  9. Cancer Research UK Manchester Institute Award [A19258]
  10. IDEX [ANR-18-IDEX-0001]
  11. INCA [PL-BIO-ICR1]
  12. [IG23179]
  13. [ANR-17-CE11-0001-01]

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This study identifies a specific population of FOLR2(+) tissue-resident macrophages in healthy mammary gland and breast cancer primary tumors, which interact with CD8(+) T cells and positively correlate with better patient survival.
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.

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