Detalle Publicación


Spatially resolved and quantitative analysis of VISTA/PD-1H as a novel immunotherapy target in human non-small cell lung cancer

Autores: Villarroel-Espindola, F.; Yu, X.; Datar, I.; Mani, N.; Fernández de Sanmamed Gutiérrez, Miguel; Velcheti, V.; Syrigos, K.; Toki, M.; Zhao, H.; Chen, L.; Herbst, R. S.; Schalper, K. A. (Autor de correspondencia)
Título de la revista: CLINICAL CANCER RESEARCH
ISSN: 1078-0432
Volumen: 24
Número: 7
Páginas: 1562 - 1573
Fecha de publicación: 2018
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 cytokeratinthorn 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, ...