Jean-Christophe Beltra, PhD Parker Bridge Fellow Biography Trained as a cancer immunologist in France, Jean-Christophe Beltra became interested in CD8 T cells. He joined the lab of Hélène Decaluwe, MD, PhD, in Montreal, Canada, to obtain an international doctorate. Supported by multiple doctoral fellowships, including from the American Association of Immunologists, he was among the first to evidence a direct impact of cytokine signals in the development of CD8 T cell exhaustion, a hypo-responsive state preventing optimal control of chronic viral infections and cancers. Convinced that CD8 T-cell exhaustion was a much more complex process than previously appreciated, in 2017 Dr. Beltra joined the lab of John Wherry, PhD, at the University of Pennsylvania with the idea that a deeper understanding of this complexity may reveal novel therapeutic opportunities. Using state-of-the-art transcriptional and epigenetic analytic approaches, Dr. Beltra found evidence of new subsets of exhausted CD8 T cells, revealing a coordinated, multistage developmental process to terminal exhaustion. This research demonstrated that exhausted CD8 T cells retain some degree of developmental flexibility that can be exploited therapeutically, notably in the context of PD-1/PDL1 blockade. As a Parker Scholar, Dr. Beltra aimed to identify new molecular pathways capable of counteracting the exhaustion program in CD8 T cells. Cytokine-derived signals appear to be key players in the process. Taking advantage of the leading expertise of the Wherry Lab, and building on PICI’s collaborative network, Dr. Beltra is using cutting-edge immunology tools and computational approaches to understand how these powerful agents shape the developmental process of CD8 T cell exhaustion. Dr. Beltra’s recent work notably showed that manipulating key cytokine pathways in TEX could strongly potentiate responses to PD-1 blockade, and even provoked epigenetic reprogramming of TEX towards better cell-states. As a Parker Bridge Fellow, Dr. Beltra is currently developing a program to exploit TEX subsets biology to identify and characterize relevant pathways for the therapeutic manipulation of TEX cells, with a particular focus on cytokine-derived signals and transcriptional circuitries with the potential of complementing PD-1-based therapy and/or reprogramming TEX cells into better cell-states. Dr. Beltra expects that his program — which capitalizes on cutting-edge concepts in our understanding of exhaustion, which he helped define — along with advanced epigenomic approaches will significantly advance PICI’s mission in designing next-generation cancer immunotherapy. He hopes this research will translate into the design of biologically relevant combinatorial approaches capable of synergizing with checkpoint blockade therapy to achieve protective immunity in a higher number of patients. Dr. Beltra holds a BSc in immunology and microbiology and an MSc in immunology and cancer from University Claude Bernard Lyon 1 in France and a PhD in the immunology of CD8 T cells from the University of Montreal. View Dr. Beltra’s YouTube Short. Education & Training 2017-Present: University of Pennsylvania, Philadelphia, PA, Postdoctoral scholar, Immunology of CD8 T cells 2017: University of Montreal, Qc, Canada, PhD, Immunology of CD8 T cells 2010: University Claude Bernard Lyon 1 (France), MSc, Immunology and Cancer 2008: University Claude Bernard Lyon 1 (France), BSc, Immunology and Microbiology Awards & Honors 2023: Parker Bridge Fellowship 2021: Parker Scholar Postdoctoral Fellowship 2017: Dean’s honor for excellent PhD defense, Faculty of Medicine, University of Montreal 2016: American Association of Immunologists (AAI), Careers in Immunology Fellowship 2014 & 2015: Department of Microbiology and Immunology, Faculty of Medicine, University of Montreal, PhD, Fellowship 2014: CHU Sainte-Justine Foundation, Excellence Doctoral Fellowship 2013: Faculty of Medicine, University of Montreal, Excellence Scholarship