PD-1 and PD-L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma

Background: Merkel cell carcinoma (MCC) is an aggressive neoplasm, which is often associated with Merkel cell polyomavirus (MCPyV). Programmed death-1 (PD-1) and its ligand PD-L1 are key players of the tumor microenvironment (TME). Methods: Fourteen paraffin-embedded tissue samples of MCC were stratified by their MCPyV detection. Apart from PD-L1 and PD-1, the TME was further characterized for the expression of CD33, FOXP3 and MxA. Results: We observed PD-1 in 2 of 12 tumors. PD-L1 expression by tumor cells was found in 7 of 8 MCPyV(+) samples and was detected particularly in the periphery. The tumor cells were surrounded by a shield of PD-L1/CD33 immune cells. Expression of PD-L1 by the tumor cells was higher in areas with a denser immune infiltrate. CD33(+) cells without direct tumor contact were PD-L1 negative. Only a low number of FOXP3(+) regulatory T-cells was admixed. Tumor cells of MCPyV(âˆ’) samples were mostly PD-L1 negative. Conclusions: Our data demonstrate that PD-L1 expression occurs in tumor and immune cells, in areas in which they are close in contact. Interferon seems to play a role in this interaction. We postulate that PD-L1(+)/CD33(+) cells shield the tumor against attacking PD-1(+) immune cells. Therefore, next to anti-PD-1/PD-L1 antibodies, blockade of CD33 seems to be a promising therapeutic approach. Â© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Berisha, A. (author)
Tronnier, M. (author)
Pfaltz, Monique C.Mittuniversitetet,Institutionen för psykologi och socialt arbete(Swepub:miun)monpfa (author)
Kempf, W. (author)
MittuniversitetetInstitutionen för psykologi och socialt arbete (creator_code:org_t)

In:Journal of cutaneous pathology: Blackwell Publishing Ltd44:9, s. 740-7460303-69871600-0560

By the author/editor: Mitteldorf, C.; Berisha, A.; Tronnier, M.; Pfaltz, Monique ...; Kempf, W.

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Health Sciences; and Other Health Sci ...

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