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Walsh, NM; Fleming, KE; Hanly, JG; Dakin Hache, K; Doucette, S; Ferrara, G; Cerroni, L.
A morphological and immunophenotypic map of the immune response in Merkel cell carcinoma.
Hum Pathol. 2016; 52(6):190-196
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Autor/innen der Med Uni Graz:
Cerroni Lorenzo
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Abstract:
The susceptibility of Merkel cell carcinoma to the host immune response has prompted a search for effective immunotherapy. CD8-positive T lymphocytes are considered key effectors of this response, but the cellular infiltrates also harbor tumor-protective agents. By developing a comprehensive morphological and immunophenotypic map of tumor-infiltrating lymphocytes (TILS) in Merkel cell carcinoma, we aimed to establish a useful template for future studies. Twenty-two cases (mean age, 79years [range, 52-95]; male-female ratio, 10:12) were studied. TILS were categorized as brisk (7), nonbrisk (9), and absent(6). Merkel cell polyomavirus (MCPyV)-positive (16) and -negative (6) cases were included, as were those with pure (18) and combined (4) morphologies. One MCPyV+ case had undergone spontaneous regression. Immunohistochemical markers included CD3, CD4, CD8, CD20, CD68, FoxP3, PD-1, and CD123. Statistical analysis used Fisher exact tests and Spearman correlations. There was a significant correlation between brisk TILs and MCPyV+ status (P=.025). CD8+ T lymphocytes predominated, were present in significantly higher proportions in brisk infiltrates (P=.003), and showed a significant predilection for the intratumoral environment (P=.003). Immune inhibitors including T regulatory cells (FOXP3+) and PD-1+ "exhausted" immunocytes were present in lower proportions. Our findings support (1) the link between a brisk immune response and MCPyV positivity, (2) the supremacy of CD8+ cells in effecting immunity, and (3) the incorporation of immune inhibitors within the global infiltrate. Efforts to therapeutically arm the "effectors" and disarm the "detractors" are well focused. These will likely have the greatest impact on MCPyV-positive cases. Copyright © 2016 Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Aged -
Aged, 80 and over -
Biomarkers, Tumor - analysis
CD8-Positive T-Lymphocytes - chemistry
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - pathology
CD8-Positive T-Lymphocytes - virology
Carcinoma, Merkel Cell - chemistry
Carcinoma, Merkel Cell - immunology
Carcinoma, Merkel Cell - pathology
Carcinoma, Merkel Cell - virology
Female -
Host-Pathogen Interactions -
Humans -
Immunohistochemistry -
Immunophenotyping - methods
Immunotherapy - methods
Lymphocyte Count -
Lymphocytes, Tumor-Infiltrating - chemistry
Lymphocytes, Tumor-Infiltrating - immunology
Lymphocytes, Tumor-Infiltrating - pathology
Lymphocytes, Tumor-Infiltrating - virology
Male -
Merkel cell polyomavirus - immunology
Middle Aged -
Phenotype -
Skin Neoplasms - chemistry
Skin Neoplasms - immunology
Skin Neoplasms - pathology
Skin Neoplasms - virology
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - pathology
Tumor Escape -
Tumor Microenvironment -

Find related publications in this database (Keywords)
Merkel cell carcinoma
Cutaneous neuroendocrine carcinoma
Tumor-infiltrating lymphocytes
TILS
Tumor-specific CD8+T cells
PD-1/PD-L1 pathway
Antitumoral immunity
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