Neuropilin-1 cooperates with PD-1 in CD8+ T cells predicting outcomes in melanoma patients treated with anti-PD1

Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by restoring antitumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Neuropilin-1 (NRP1) is a transmembrane glycoprotein required for nervous system and angiogenesis embryonic development, also expressed in immune cells. Wehypothesized that NRP1 could be an immune checkpoint co- receptor modulating CD8(+) T cells activity in the context of the antitumor immune response. Here, we show that NRP1 is recruited in the cytolytic synapse of PD1(+)CD8(+) T cells, cooperates and enhances PD-1 activity. In mice, CD8(+) T cells specific deletion of Nrp1 improves anti-PD1 antibody antitumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8(+) T cells predicts poor outcome of patients treated with antiPD1. NRP1 is a promising target to overcome resistance to anti-PD1 therapies.

Automated summary

Targeting immune checkpoints, such as PD1, has improved survival in cancer patients. However, most patients still relapse or are refractory to these therapies. This study found that NRP1, a transmembrane glycoprotein, plays a crucial role in modulating the activity of CD8(+) T cells in the antitumor immune response.