Neuropilin-1 is a T cell memory checkpoint limiting long-term antitumor immunity.

ABSTRACT: Robust CD8⁺ T cell memory is essential for long-term protective immunity but is often compromised in cancer, where T cell exhaustion leads to loss of memory precursors. Immunotherapy via checkpoint blockade may not effectively reverse this defect, potentially underlying disease relapse. Here we report that mice with a CD8⁺ T cell-restricted neuropilin-1 (NRP1) deletion exhibited substantially enhanced protection from tumor rechallenge and sensitivity to anti-PD1 immunotherapy, despite unchanged primary tumor growth. Mechanistically, NRP1 cell-intrinsically limited the self-renewal of the CD44⁺PD1⁺TCF1⁺TIM3^- progenitor exhausted T cells, which was associated with their reduced ability to induce c-Jun/AP-1 expression on T cell

SUBMITTER: Liu C 

PROVIDER: S-EPMC7442600 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature