小柯机器人

美国匹兹堡大学Dario A. A. Vignali团队的研究发现Neuropilin-1是T细胞记忆检查点，可限制长期抗肿瘤免疫力。这一研究成果于2020年7月13日在线发表在《自然—免疫学》上。

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

Author: Chang Liu, Ashwin Somasundaram, Sasikanth Manne, Angela M. Gocher, Andrea L. Szymczak-Workman, Kate M. Vignali, Ellen N. Scott, Daniel P. Normolle, E. John Wherry, Evan J. Lipson, Robert L. Ferris, Tullia C. Bruno, Creg J. Workman, Dario A. A. Vignali

Issue&Volume: 2020-07-13

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 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.

DOI: 10.1038/s41590-020-0733-2

Source: https://www.nature.com/articles/s41590-020-0733-2

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex