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PD ‐1 and PD‐L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma
Author(s) -
Mitteldorf Christina,
Berisha Arbeneshe,
Tronnier Michael,
Pfaltz Monique C.,
Kempf Werner
Publication year - 2017
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.12973
Subject(s) - tumor microenvironment , foxp3 , immune system , merkel cell polyomavirus , immune checkpoint , merkel cell carcinoma , pd l1 , cancer research , biology , t cell , immunotherapy , pathology , immunology , medicine , 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 (−) 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.