Merkel cell carcinoma expresses the immunoregulatory ligand CD200 and induces immunosuppressive macrophages and regulatory T cells.
Maria Rita Gaiser, Cleo-Aron Weis, Timo Gaiser, Hong Jiang, Kristina Buder-Bakhaya, Esther Herpel, Arne Warth, Ying Xiao, Lingling Miao, Isaac Brownell
Author Information
Maria Rita Gaiser: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
Cleo-Aron Weis: Department of Dermatology, Heidelberg University Hospital, Heidelberg, Germany.
Timo Gaiser: Department of Dermatology, Heidelberg University Hospital, Heidelberg, Germany.
Hong Jiang: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA.
Kristina Buder-Bakhaya: National Center for Tumor Diseases and Department of Dermatology, University Hospital Heidelberg, Ruprecht-Karl University of Heidelberg, Heidelberg, Germany.
Esther Herpel: Tissue Bank of the National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.
Arne Warth: Tissue Bank of the National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.
Ying Xiao: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA.
Lingling Miao: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA.
Isaac Brownell: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA.
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 mRNA expression in MCC tumors, and CD200 immunostaining was demonstrated on 95.5% of MCC tumors. CD200R-expressing myeloid cells were present in the MCCtumor 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 MCCtumor cells , this treatment may provide a novel immunotherapy for MCC independent of PD-1/PD-L1 blockade.
