A morphological and immunophenotypic map of the immune response in Merkel cell carcinoma
| Autor: | Kirsten E. Fleming, Steve Doucette, Noreen M. Walsh, Lorenzo Cerroni, Gerardo Ferrara, Kelly Dakin Hache, John G. Hanly |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Skin Neoplasms medicine.medical_treatment Merkel cell polyomavirus CD8-Positive T-Lymphocytes T-Lymphocytes Regulatory Immunophenotyping Pathology and Forensic Medicine 03 medical and health sciences Lymphocytes Tumor-Infiltrating 0302 clinical medicine Immune system Biomarkers Tumor Tumor Microenvironment medicine Humans Lymphocyte Count Aged Aged 80 and over biology Merkel cell carcinoma Tumor-infiltrating lymphocytes FOXP3 Immunotherapy Middle Aged biology.organism_classification medicine.disease Immunohistochemistry Carcinoma Merkel Cell Phenotype 030104 developmental biology 030220 oncology & carcinogenesis Host-Pathogen Interactions Immunology Female Tumor Escape CD8 |
| Zdroj: | Human Pathology. 52:190-196 |
| ISSN: | 0046-8177 |
| DOI: | 10.1016/j.humpath.2016.02.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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