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

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...

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Main Authors: Gaiser, Maria (Author) , Weis, Cleo-Aron Thias (Author) , Gaiser, Timo (Author) , Buder-Bakhaya, Kristina (Author) , Herpel, Esther (Author) , Warth, Arne (Author)
Format: Article (Journal)
Language:English
Published: 08 Feb 2018
In: OncoImmunology
Year: 2018, Volume: 7, Issue: 5
ISSN:2162-402X
DOI:10.1080/2162402X.2018.1426517
Online Access:Verlag, Volltext: https://doi.org/10.1080/2162402X.2018.1426517
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Author Notes:Maria Rita Gaiser, Cleo-Aron Weis, Timo Gaiser, Hong Jiang, Kristina Buder-Bakhaya, Esther Herpel, Arne Warth, Ying Xiao, Lingling Miao and Isaac Brownell

MARC

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520 |a 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. 
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