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

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. BigorgneHéloise 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

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    4 Citations (Scopus)

    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.

    Original languageEnglish
    Article number104353
    JournaliScience
    Volume25
    Issue number6
    DOIs
    Publication statusPublished - 17 Jun 2022

    Keywords

    • Cancer
    • Immunology

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