Ramos and Missolo-Koussou et al. assessed cellular heterogeneity within the CD14+ compartment isolated from metastatic lymph nodes and primary breast tumors, and identified TREM2+ and FOLR2+ TAMs, evolutionarily conserved between human and mouse. TREM2+ TAMs were in tumor nests and increased with tumor development, whereas FOLR2+ macrophages were tissue-resident, were present in healthy mammary glands, and persisted during tumor development. FOLR2+ macrophages correlated with better survival in breast cancer, were localized in the tumor stroma near blood vessels, clustered with CD8+ T cells, and could trigger CD8+ T cell activation.
Contributed by Shishir Pant
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.
Author Info: (1) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (2) PSL University, Institut Curie Research Center,
Author Info: (1) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (2) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (3) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (4) Cancer Inflammation and Immunity Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Manchester, UK. (5) Department of Pathology, University of Brescia, Brescia 25123, Italy. (6) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (7) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (8) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (9) PSL University, Institut Curie Research Center, INSERM U932, 75005 Paris, France. (10) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (11) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (12) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (13) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (14) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (15) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (16) PSL University, Institut Curie Research Center, Institut Curie Genomics of Excellence Platform, 75005 Paris, France. (17) PSL University, Institut Curie Research Center, Institut Curie Genomics of Excellence Platform, 75005 Paris, France. (18) PSL University, Institut Curie Research Center, Institut Curie Genomics of Excellence Platform, 75005 Paris, France. (19) PSL University, Institut Curie Hospital, Department of Pathology, 75005 Paris, France. (20) PSL University, Institut Curie Hospital, Department of Pathology, 75005 Paris, France. (21) PSL University, Institut Curie Hospital, Department of Pathology, 75005 Paris, France. (22) PSL University, Institut Curie Hospital, Department of Pathology, 75005 Paris, France. (23) PSL University, Institut Curie Hospital, Department of Surgery, 75005 Paris, France. (24) Universit Paris-Saclay, Institut Gustave Roussy, INSERM U1015, Villejuif, France. (25) Universit Paris-Saclay, Institut Gustave Roussy, INSERM U1015, Villejuif, France; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore. (26) University of Paris, Institut Cochin, INSERM U1016, CNRS UMR 8104, 75014 Paris, France. (27) University of Paris, Institut Cochin, INSERM U1016, CNRS UMR 8104, 75014 Paris, France. (28) INSERM, Sorbonne Universit, Universit de Paris, Centre de Recherche des Cordeliers, Laboratory of Integrative Cancer Immunology, Paris, France. (29) INSERM, Sorbonne Universit, Universit de Paris, Centre de Recherche des Cordeliers, Laboratory of Integrative Cancer Immunology, Paris, France. (30) Cancer Inflammation and Immunity Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Manchester, UK. (31) PSL University, Institut Curie Research Center, INSERM U932, 75005 Paris, France; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. (32) Universit de Paris, Centre for Inflammation Research, CNRS ERL8252, INSERM1149, Paris, France. (33) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. (34) PSL University, Institut Curie Research Center, INSERM U932 & SiRIC, Translational Immunotherapy Team, 75005 Paris, France. Electronic address: julie.helft@inserm.fr.
