PD-1 and PD-L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma.
J Cutan Pathol
; 44(9): 740-746, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28569410
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Carcinoma de Célula de Merkel
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Biomarcadores Tumorais
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Microambiente Tumoral
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Antígeno B7-H1
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Receptor de Morte Celular Programada 1
Limite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article