342 The Implications of High Expression of VISTA, a Negative Check Point Regulator, on Prognosis Across Malignant Solid Tumors: a Systematic Review and Meta-Analysis

• Published in: Journal of clinical and translational science 2023-04, Vol.7 (s1), p.101-102
• Main Authors: Martin, Alexander S, Salei, Yana V, Lalla, Mumtu, Sebastiani, Paola, Morin, Rebecca A., Martell, Robert E, Trinquart, Ludovic
• Format: Article
• Language: English
• Subjects: Cell activation; Cohort analysis; Immune checkpoint; Lymphocytes T; Medical prognosis; Mesothelioma; Meta-analysis; Population studies; Precision Medicine/Health; Prognosis; Protein expression; Reviews; Signal transduction; Solid tumors; Systematic review; Tumor microenvironment; Tumors
• ISSN: 2059-8661; 2059-8661
• DOI: 10.1017/cts.2023.386

OBJECTIVES/GOALS: Targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) signaling pathway has been suggested as a promising approach for overcoming resistance to current immune checkpoint therapies in advanced cancer. This review will synthesize the rapidly-expanding literature on VISTA protein expression on prognosis in various cancers. METHODS/STUDY POPULATION: To determine the prognostic significance of high VISTA expression across treatment-naïve malignant tumors, a systematic review and meta-analysis will be performed of published cohort studies which measured VISTA protein expression on solid tumors. Primary and secondary outcome endpoints of overall survival (OS) and disease-specific survival (DSS) will be compared across cohort studies using a random effects model to calculate pooled hazard ratios (HRs) for each time-to-event end point with 95% CIs. For articles that only provide Kaplan-Meier (KM) curves, the Engauge Digitizer software will be used to measure the time and survival probability coordinates on the KM curves to estimate the HRs. Correlations of VISTA expression and clinicopathological characteristics will be evaluated by pooled risk ratios. RESULTS/ANTICIPATED RESULTS: A search of 4 electronic databases including Pubmed, Embase, Web of Science and Cochrane resulted in 5578 publications of which 66 containing a broad spectrum of malignant solid tumors will undergo full-text review for study inclusion. Tumor types most represented with at least 3 articles include lung, pancreas, skin, head & neck, colorectal, mesothelioma, cervix, soft tissue, breast, liver and ovarian. Our working hypothesis is that the pooled HR for high VISTA expression on overall survival will be approaching 1.0 given conflicting reports across the cancer literature. Risk of bias will be assessed across studies. Quantifications of heterogeneity will be assessed by visual exploration of forest plots as well as by multiple statistical metrics including the Q statistic and the I²coefficient. DISCUSSION/SIGNIFICANCE: The results of this systematic review and meta-analysis will provide a more comprehensive understanding of VISTA’s prognostic role both across all malignant tumors and for subgroups of similar tumor types which may impact the types of tumors and tumor microenvironments selected for early trials of anti-VISTA therapy.