학술논문
Neuropilin-1 cooperates with PD-1 in CD8+ T cells predicting outcomes in melanoma patients treated with anti-PD1
Document Type
article
Author
Julien Rossignol; Zakia Belaid; Guillemette Fouquet; Flavia Guillem; Rachel Rignault; Pierre Milpied; Amédée Renand; Tereza Coman; Maud D’Aveni; Michael Dussiot; Elia Colin; Jonathan Levy; Caroline Carvalho; Nicolas Goudin; Nicolas Cagnard; Francine Côté; Joel Babdor; Kanit Bhukhai; Laura Polivka; Amélie E. Bigorgne; Héloise Halse; Aurélien Marabelle; Séverine Mouraud; Yves Lepelletier; Thiago T. Maciel; Marie-Thérèse Rubio; Delphine Heron; Caroline Robert; Isabelle Girault; Doris Lebeherec; Jean-Yves Scoazec; Ivan Moura; Louise Condon; Mirjana Weimershaus; Franck Pages; Jean Davoust; David Gross; Olivier Hermine
Source
iScience, Vol 25, Iss 6, Pp 104353- (2022)
Subject
Language
English
ISSN
2589-0042
Abstract
Summary: 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.