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


Mitteldorf, Christina; Berisha, Arbeneshe; Tronnier, Michael; Pfaltz, Monique C; Kempf, Werner (2017). PD-1 and PD-L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma. Journal of Cutaneous Pathology, 44(9):740-746.

Abstract

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(-) 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.

Abstract

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(-) 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Klinik für Konsiliarpsychiatrie und Psychosomatik
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Merkel cell carcinoma; PD-1; PD-L1; myeloid-derived suppressor cells; tumor microenvironment
Language:English
Date:2017
Deposited On:21 Dec 2017 16:46
Last Modified:19 Feb 2018 09:43
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0303-6987
OA Status:Closed
Publisher DOI:https://doi.org/10.1111/cup.12973
PubMed ID:28569410

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