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

Fiche publication

Date publication

juin 2022

Journal

iScience

Auteurs

Membres identifiés du Cancéropôle Est :
Pr RUBIO Marie Thérèse , Dr D'AVENI-PINEY Maud

Tous les auteurs :
Rossignol J, Belaid Z, Fouquet G, Guillem F, Rignault R, Milpied P, Renand A, Coman T, D'Aveni M, Dussiot M, Colin E, Levy J, Carvalho C, Goudin N, Cagnard N, Côté F, Babdor J, Bhukhai K, Polivka L, Bigorgne AE, Halse H, Marabelle A, Mouraud S, Lepelletier Y, Maciel TT, Rubio MT, Heron D, Robert C, Girault I, Lebeherec D, Scoazec JY, Moura I, Condon L, Weimershaus M, Pages F, Davoust J, Gross D, Hermine O

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35874918

Résumé

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 PD1CD8 T cells, cooperates and enhances PD-1 activity. In mice, CD8 T cells specific deletion of 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.