Merkel cell carcinoma expresses the immunoregulatory ligand CD200 and induces immunosuppressive macrophages and regulatory T cells. (4th May 2018)

• Record Type: Journal Article
• Authors: Gaiser, Maria Rita; Weis, Cleo-Aron; Gaiser, Timo; Jiang, Hong; Buder-Bakhaya, Kristina; Herpel, Esther; Warth, Arne; Xiao, Ying; Miao, Lingling; Brownell, Isaac
• Is Part Of: Oncoimmunology. Volume 7:Number 5(2018)
• Publication Date: 2018-05-04
• Subjects: CD200 -- Merkel cell carcinoma -- immune checkpoint inhibitor -- M2 macrophage -- regulatory T cell; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2018.1426517
• Languages: English
• ISSNs: 2162-402X

Abstract

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.