Grant: Master's Award: Canada Graduate Scholarships

Malignant Pleural Mesothelioma (MPM) is a rare and lethal lung cancer linked to the inhalation of asbestos fibres. MPM has a bleak 5-year survival rate of 7% in Canada and minimal effective treatment options. Despite advancements in anti-PD1 therapies in other lung cancer types, the epithelioid subtype of MPM (eMPM) remains highly resistant to current immunotherapy. Still, there are large numbers of immune checkpoint markers that have yet to be explored for immune therapy. This proposed study focuses on the role of V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA). VISTA is an emerging immune cell negative checkpoint regulator with heightened expression in eMPM. Previously, VISTA has been shown to inhibit T-cell activation and prevent T-cell migration from the bloodstream, suggesting a pro-tumor function and potential resistance mechanism to current immunotherapy. However, it is unclear which cell types express VISTA in MPM and whether response to therapy correlates with certain cell type expression patterns or general VISTA expression. Visualizing VISTA’s single-cell expression and interactions could uncover specific prognostic patterns. This study will use multiplex immunofluorescence with advanced spatial characterization tools to match VISTA expression to cell lineage markers. Leveraging the opportunity to access biopsies and outcomes from participants with MPM in the IND227 clinical study who received Pembrolizumasb with chemotherapy, this study will compare pre-treatment VISTA expression to treatment response. Results may identify patterns that provide predictive and prognostic information for using VISTA as a biomarker and inform the feasibility of anti-VISTA immune checkpoint blockade.