Paolo Dario Angelo Vignali PhDMedical Student, Department of Immunology, University of Pittsburgh School of Medicine and Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania
Paolo Vignali, PhD, is a fourth-year medical student at the University of Pittsburgh School of Medicine. His dissertation research describes how tumor hypoxia interferes with effective immune responses and circumvents immune cell reactivation following checkpoint blockade. Specifically, he has shown how tumor hypoxia accelerates differentiation of effector T cells to a dysfunctional state known as ‘exhaustion’. High levels of exhausted T cells in solid tumors have been shown to correlate with poor outcomes, yet this mechanism remains poorly understood. Paolo advanced this model by demonstrating how hypoxic conditions disrupt metabolic pathways and lead to rapid differentiation of T cells to an exhausted state. Further, he showed that T cells exposed to tumor hypoxia upregulate the inhibitory molecule, CD39, resulting in local suppression of local immune responses. Reversal of tumor hypoxia or deletion of CD39 was sufficient to decrease exhausted T cell concentrations and sensitize treatment refractory tumors to checkpoint blockade therapy. Paolo is currently applying to Dermatology residency programs in the United States and plans to continue to develop his interests in academic research.