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

2022; Cell Press; Volume: 25; Issue: 6 Linguagem: Inglês

10.1016/j.isci.2022.104353

2589-0042

Julien Rossignol, Zakia Belaid, Guillemette Fouquet, Flavia Guillem, Rachel Rignault, Pierre Milpied, Amédée Renand, Téreza Coman, Maud D’Aveni, Michaël Dussiot, Elia Colin, Jonathan Lévy, Caroline Carvalho, Nicolas Goudin, Nicolas Cagnard, Francine Côté, Joël Babdor, Kanit Bhukhai, Laura Polivka, Amélie Bigorgne, Heloise M. Halse, Aurélien Marabelle, Séverine Mouraud, Yves Lepelletier, Thiago Trovati Maciel, Marie‐Thérèse Rubio, Delphine Héron, Caroline Robert, Isabelle Girault, Doris Lebeherec, Jean‐Yves Scoazec, Ivan Cruz Moura, Louise Condon, Mirjana Weimershaus, Franck Pagès, Jean Davoust, David‐Alexandre Gross, Olivier Hermine,

Cancer, Stress, Anesthesia, and Immune Response

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.