Abstract 5657: Objective measurement and significance of VISTA (PD-1H) expression in non-small cell lung cancer (NSCLC)

Abstract

Abstract Introduction: VISTA (PD-1H) is a member of the B7 family of immune co-regulatory molecules and has been proposed as a novel anti-cancer immunotherapy target. The intra- and extracellular domains of VISTA show homology to PD-1 and PD-L1, respectively, suggesting a role in anti-tumor immune evasion. The expression of VISTA, its association with PD-1 axis components and biological role in human NSCLC are unknown. Methods: Using multiplex quantitative immunofluorescence (QIF), we simultaneously measured the levels of VISTA (clone D1L2G, CST), PD-L1 (clone 405.9A11, CST) and PD-1 (clone EH33, CST) protein in 732 stage I-IV NSCLCs from 3 retrospective collections represented in tissue microarray format (cohort #1 [n=297, Yale], cohort #2 [n=329, Greece]; and cohort #3 [n=106, Yale]). To evaluate the tumor tissue distribution, VISTA was also selectively measured in cytokeratin+ tumor cells, CD3+ T-cells, CD4+ T-helper cells, CD8+ cytotoxic T-cells and CD20+ B-lymphocytes. Associations between the marker levels, clinico-pathological-molecular variables and survival were studied. Results: VISTA protein was detected in all NSCLCs, showed a membranous staining pattern and was localized predominantly in the tumor cells in 27.4% of cases; and in the stromal compartment in 98.5%. Although VISTA was detected in all major tumor infiltrating lymphocyte (TIL) subsets, the signal was higher in CD20+ B-cells than in CD3+ T-lymphocytes (P<0.05); and in CD4+ helper than in CD8+ cytotoxic T-cells (P<0.001). Using the median score as cut point, elevated VISTA in tumor and/or stromal cells was significantly associated with high PD-L1, PD-1 protein expression and increased CD8+TILs in the cohorts (P<0.001 - P<0.05). No consistent association between VISTA levels and age, gender, smoking status, specific NSCLC histology, stage, EGFR/KRAS mutations and overall survival was found. Conclusion: VISTA is expressed in the majority of NSCLCs and shows differential distribution in tumor/stromal cells and TIL subsets, suggesting a complex function as a ligand and receptor. Elevated expression of VISTA in NSCLC is associated with increased PD-1 axis targets and cytotoxic T-cell density, indicating its possible modulation by pro-inflammatory signals. Our results support VISTA as a candidate target for anti-cancer immunotherapy in NSCLC alone or in combination with PD-1 axis blockers. Citation Format: Franz Villarroel-Espindola, Ila J. Datar, Vamsidhar Velcheti, David L. Rimm, Roy S. Herbst, Kurt A. Schalper. Objective measurement and significance of VISTA (PD-1H) expression in non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5657. doi:10.1158/1538-7445.AM2017-5657