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Immuno-oncology
Oral
Chang Liu, PhD
Postdoctoral fellow
Department of Immunology, School of Medicine, University of Pittsburgh
Ashwin Somasundaram, PhD
Postdoctoral fellow
University of Pittsburgh
Sasikanth Manne, MSc
Research Specialist
Penn Institute for Immunology, University of Pennsylvania
Andrea Szymczak-Workman, PhD
Research Associate
Department of Immunology, University of Pittsburgh
Angela Gocher, PhD
Postdoctoral fellow
University of Pittsburgh
Tullia Bruno, PhD
Research Assistant Professor
University of Pittsburgh
E. John Wherry, PhD
Professor
Penn Institute for Immunology, University of Pennsylvania
Creg Workman, PhD
Research Assistant Professor
University of Pittsburgh
Dario Vignali, PhD
Professor
University of Pittsburgh
CD8+ T cell memory is pivotal for long-term protective immunity, but often impaired in the tumor setting, partially due to extensive T cell exhaustion and loss of memory precursors, which is not reversed by checkpoint blockade immunotherapy. It is, however, incompletely understood how T cell exhaustion is maintained, which in turn impedes functional CD8 memory development. Here we report that mice with CD8+ T cell-restricted deficiency of Neuropilin 1 (NRP1) showed significantly enhanced protection from re-challenged B16.F10 tumors, despite unchanged primary tumor growth. NRP1 acted on multiple inhibitory receptors (IRs)-expressing CD8+ T cells to reinforce their exhaustion status and restrain the potential of memory differentiation, by repressing the Id3-dependent transcription program. These data reveal NRP1 as a unique “immune checkpoint” contributing to the lineage stability and blocking the memory conversion in the exhausted CD8+ T cells, a mechanism of action that is distinct from that of well-known immune checkpoints (PD1, CTLA4, LAG3). Blockade of checkpoint inhibitors of T cell memory may be necessary to achieve durable anti-tumor immunity.