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  • Cancer cell CCR2 orchestrates suppression of the adaptive immune response.

Cancer cell CCR2 orchestrates suppression of the adaptive immune response.

The Journal of experimental medicine (2020-07-16)
Miriam R Fein, Xue-Yan He, Ana S Almeida, Emilis Bružas, Arnaud Pommier, Ran Yan, Anaïs Eberhardt, Douglas T Fearon, Linda Van Aelst, John Erby Wilkinson, Camila O Dos Santos, Mikala Egeblad
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Brefeldin A, ≥99% (HPLC and TLC), BioXtra, for molecular biology
Sigma-Aldrich
Eosin Y Solution, Alcoholic