You are invited to a "Free Friday Seminar" on 29 May at 1200 hrs EDT sponsored by the Latin Comparative Pathology Group. This virtual seminar is entitled "Pathology of immune-mediated drug-induced liver injury in immuno-oncology checkpoint inhibitor combination", and is presented by Timothy Affolter, DVM, PhD, DACVP of Global Pathology, Pfizer Drug Safety Research and Development, La Jolla, CA. Immune checkpoint inhibitors (CPI) are the cornerstone drugs of immuno-oncology and generally act by promoting T cell activation with subsequent tumor cell killing. Current animal models under predict the incidence and severity of immune-related adverse events observed with CPI drug combinations in the clinic. We have developed a novel mouse model that closely recapitulates these immune-mediated adverse events in the setting of a combined checkpoint blockade. Co-administration of a CTLA4 blocking antibody and an IDO1 inhibitor to PD1 knockout mice drives inflammation and necrosis in the liver, and more sporadically in other tissues, with histopathologic phenotypes similar to what has been reported clinically. Immunophenotyping of the inflammation revealed an expanded oligoclonal population of CD8+ T cells, with elevated ICOS and CD44 expression. Several novel technologies including laser capture microscopy, digital image analysis, and single cell transcriptomic analysis were used to further characterize the expression of several activation and exhaustion markers in infiltrating CD8+ T cell population. Global depletion of CD8+ T cells attenuated CPI-induced liver injury. Register in advance for this webinar: https://us02web.zoom.us/webinar/register/WN_hg77GG38T_2Jh5Kg7m6Hog?fbclid=Iw... <https://us02web.zoom.us/webinar/register/WN_hg77GG38T_2Jh5Kg7m6Hog?fbclid=Iw...>