Τίτλος:
Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel
Immunotherapy Target in Human Non-Small Cell Lung Cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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, 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. (C) 2017 AACR.
Συγγραφείς:
Villarroel-Espindola, Franz
Yu, Xiaoqing
Datar, Ila
Mani,
Nikita
Sanmamed, Miguel
Velcheti, Vamsidhar
Syrigos,
Konstantinos
Toki, Maria
Zhao, Hongyu
Chen, Lieping and
Herbst, Roy S.
Schalper, Kurt A.
Περιοδικό:
Clinical Cancer Research
Εκδότης:
AMER ASSOC CANCER RESEARCH
DOI:
10.1158/1078-0432.CCR-17-2542
