| First Author | Liu C | Year | 2020 |
| Journal | Nat Immunol | Volume | 21 |
| Issue | 9 | Pages | 1010-1021 |
| PubMed ID | 32661362 | Mgi Jnum | J:299786 |
| Mgi Id | MGI:6490669 | Doi | 10.1038/s41590-020-0733-2 |
| Citation | Liu C, et al. (2020) Neuropilin-1 is a T cell memory checkpoint limiting long-term antitumor immunity. Nat Immunol 21(9):1010-1021 |
| abstractText | 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 receptor restimulation, a mechanism that may contribute to terminal T cell exhaustion at the cost of memory differentiation in wild-type tumor-bearing hosts. These data indicate that blockade of NRP1, a unique 'immune memory checkpoint', may promote the development of long-lived tumor-specific Tmem that are essential for durable antitumor immunity. |
