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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| Autores principales: | , , , , , |
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| Formato: | Article (Journal) |
| Lenguaje: | inglés |
| Publicado: |
08 Feb 2018
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| In: |
OncoImmunology
Year: 2018, Volumen: 7, Número: 5 |
| ISSN: | 2162-402X |
| DOI: | 10.1080/2162402X.2018.1426517 |
| Acceso en línea: | Verlag, Volltext: https://doi.org/10.1080/2162402X.2018.1426517
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| Notas de Autor: | Maria Rita Gaiser, Cleo-Aron Weis, Timo Gaiser, Hong Jiang, Kristina Buder-Bakhaya, Esther Herpel, Arne Warth, Ying Xiao, Lingling Miao and Isaac Brownell |
| Sumario: | 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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| Notas: | Gesehen am 08.08.2019 |
| Descripción Física: | Online Resource |
| ISSN: | 2162-402X |
| DOI: | 10.1080/2162402X.2018.1426517 |