Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non-Small Cell Lung Cancer.

Autor:	Villarroel-Espindola F; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Yu X; Department of Public Health, Yale School of Medicine, New Haven, Connecticut., Datar I; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Mani N; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Sanmamed M; Immunobiology, Yale School of Medicine, New Haven, Connecticut., Velcheti V; Solid Tumor Oncology, Cleveland Clinic Foundation, Cleveland, Ohio., Syrigos K; Oncology Unit GPP, Athens School of Medicine, Greece., Toki M; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Zhao H; Department of Public Health, Yale School of Medicine, New Haven, Connecticut., Chen L; Immunobiology, Yale School of Medicine, New Haven, Connecticut., Herbst RS; Medical Oncology and Yale Cancer Center, New Haven, Connecticut., Schalper KA; Department of Pathology, Yale School of Medicine, New Haven, Connecticut. kurt.schalper@yale.edu.; Medical Oncology and Yale Cancer Center, New Haven, Connecticut.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2018 Apr 01; Vol. 24 (7), pp. 1562-1573. Date of Electronic Publication: 2017 Dec 04.
DOI:	10.1158/1078-0432.CCR-17-2542
Abstrakt:	Purpose: Determine the localized expression pattern and clinical significance of VISTA/PD-1H in human non-small cell lung cancer (NSCLC). Experimental Design: Using multiplex quantitative immunofluorescence (QIF), we performed localized measurements of VISTA, PD-1, and PD-L1 protein in 758 stage I-IV NSCLCs from 3 independent cohorts represented in tissue microarray format. The targets were selectively measured in cytokeratin + tumor epithelial cells, CD3 + T cells, CD4 + T-helper cells, CD8 + cytotoxic T cells, CD20 + B lymphocytes and CD68 + tumor-associated macrophages. We determined the association between the targets, clinicopathological/molecular variables and survival. Genomic analyses of lung cancer cases from TCGA were also performed. Results: VISTA protein was detected in 99% of NSCLCs with a predominant membranous/cytoplasmic staining pattern. Expression in tumor and stromal cells was seen in 21% and 98% of cases, respectively. The levels of VISTA were positively associated with PD-L1, PD-1, CD8 + T cells and CD68 + macrophages. VISTA expression was higher in T-lymphocytes than in macrophages; and in cytotoxic T cells than in T-helper cells. Elevated VISTA was associated with absence of EGFR mutations and lower mutational burden in lung adenocarcinomas. Presence of VISTA in tumor compartment predicted longer 5-year survival. Conclusions: VISTA is frequently expressed in human NSCLC and shows association with increased tumor-infiltrating lymphocytes, PD-1 axis markers, specific genomic alterations and outcome. These results support the immunomodulatory role of VISTA in human NSCLC and suggests its potential as therapeutic target. Clin Cancer Res; 24(7); 1562-73. ©2017 AACR . (©2017 American Association for Cancer Research.)
Databáze:	MEDLINE
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