Neuropilin-1 cooperates with PD-1 in CD8+ T cells predicting outcomes in melanoma patients treated with anti-PD1 - Archive ouverte HAL Access content directly
Journal Articles iScience Year : 2022

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

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Jonathan Levy
Caroline Robert
  • Function : Author
  • PersonId : 1019532
Franck Pagès
  • Function : Author
  • PersonId : 1076296
Jean Davoust
  • Function : Author
  • PersonId : 1179460
David Gross

Abstract

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. We hypothesized 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 anti-PD1. NRP1 is a promising target to overcome resistance to anti-PD1 therapies.

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Origin : Publication funded by an institution

Dates and versions

hal-03842485 , version 1 (09-11-2022)

Licence

Attribution - NonCommercial - NoDerivatives - CC BY 4.0

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Julien Rossignol, Zakia Belaid, Guillemette Fouquet, Flavia Guillem, Rachel Rignault, et al.. Neuropilin-1 cooperates with PD-1 in CD8+ T cells predicting outcomes in melanoma patients treated with anti-PD1. iScience, 2022, 25 (6), pp.104353. ⟨10.1016/j.isci.2022.104353⟩. ⟨hal-03842485⟩
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