Merkel cell carcinoma expresses the immunoregulatory ligand CD200 and induces immunosuppressive macrophages and regulatory T cells.

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Merkel cell carcinoma expresses the immunoregulatory ligand CD200 and induces immunosuppressive macrophages and regulatory T cells.

Oncoimmunology. 2018;7(5):e1426517

Authors: Gaiser MR, Weis CA, Gaiser T, Jiang H, Buder-Bakhaya K, Herpel E, Warth A, Xiao Y, Miao L, Brownell I

Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer that responds to PD-1/PD-L1 immune checkpoint inhibitors. CD200 is another checkpoint modulator whose receptor is found on tumor-promoting myeloid cells, including M2 macrophages. We found high CD200 mRNA expression in MCC tumors, and CD200 immunostaining was demonstrated on 95.5% of MCC tumors. CD200R-expressing myeloid cells were present in the MCC tumor microenvironment. MCC-associated macrophages had a higher average CD163:CD68 staining ratio (2.67) than controls (1.13), indicating an immunosuppressive M2 phenotype. Accordingly, MCC tumors contained increased densities of FOXP3+ regulatory T-cells. Intravenous administration of blocking anti-CD200 antibody to MCC xenograft mice revealed specific targeting of drug to tumor. In conclusion, MCC are highly CD200 positive and associated with immunosuppressive M2 macrophages and regulatory T-cells. As anti-CD200 antibody effectively targets CD200 on MCC tumor cells in vivo, this treatment may provide a novel immunotherapy for MCC independent of PD-1/PD-L1 blockade.

PMID: 29721394 [PubMed]

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