Cancer cell CCR2 orchestrates suppression of the adaptive immune response.
Fiche publication
Date publication
octobre 2020
Journal
The Journal of experimental medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Dr POMMIER Arnaud
Tous les auteurs :
Fein MR, He XY, Almeida AS, Bružas E, Pommier A, Yan R, Eberhardt A, Fearon DT, Van Aelst L, Wilkinson JE, Dos Santos CO, Egeblad M
Lien Pubmed
Résumé
C-C chemokine receptor type 2 (CCR2) is expressed on monocytes and facilitates their recruitment to tumors. Though breast cancer cells also express CCR2, its functions in these cells are unclear. We found that Ccr2 deletion in cancer cells led to reduced tumor growth and approximately twofold longer survival in an orthotopic, isograft breast cancer mouse model. Deletion of Ccr2 in cancer cells resulted in multiple alterations associated with better immune control: increased infiltration and activation of cytotoxic T lymphocytes (CTLs) and CD103+ cross-presenting dendritic cells (DCs), as well as up-regulation of MHC class I and down-regulation of checkpoint regulator PD-L1 on the cancer cells. Pharmacological or genetic targeting of CCR2 increased cancer cell sensitivity to CTLs and enabled the cancer cells to induce DC maturation toward the CD103+ subtype. Consistently, Ccr2-/- cancer cells did not induce immune suppression in Batf3-/- mice lacking CD103+ DCs. Our results establish that CCR2 signaling in cancer cells can orchestrate suppression of the immune response.
Mots clés
Adaptive Immunity, immunology, Animals, Apoptosis, B7-H1 Antigen, metabolism, Dendritic Cells, immunology, Female, Histocompatibility Antigens Class I, metabolism, Immune Tolerance, immunology, Interferons, metabolism, Mammary Neoplasms, Experimental, immunology, Mice, Mice, Inbred C57BL, Receptors, CCR2, immunology, T-Lymphocytes, Cytotoxic, immunology
Référence
J Exp Med. 2020 10 5;217(10):