Regulation of antitumour CD8 T-cell immunity and checkpoint blockade immunotherapy by Neuropilin-1

• DOI: 10.1038/s41467-019-11280-z
• Publication Date: 2019-07-26T10:03:04Z
• Authors: Marine Leclerc; Elodie Voilin; Gwendoline Gros; Stéphanie Corgnac; Vincent de Montpr...; Pierre Validire; Georges Bismuth; Fathia Mami-Chouaib
• Keywords: Immune checkpoint; Cancer Immunotherapy

Neuropilin-1 (Nrp-1) is a marker for murine CD4+FoxP3+ regulatory T (Treg) cells, subset of human CD4+ Treg and population CD8+ cells infiltrating certain solid tumours. However, whether Nrp-1 regulates tumour-specific CD8 T-cell responses still unclear. Here we show that defines displaying PD-1hi status lung cancer. Interaction with its ligand semaphorin-3A inhibits migration lytic function cytotoxic lymphocytes. In vivo, Nrp-1+PD-1hi tumour-infiltrating lymphocytes (TIL) in B16F10 melanoma are enriched tumour-reactive exhibiting an exhausted state, expressing Tim-3, LAG-3 CTLA-4 inhibitory receptors. Anti-Nrp-1 neutralising antibodies enhance the cytotoxicity TIL ex while vivo immunotherapeutic blockade synergises anti-PD-1 to proliferation, tumour control. Thus, could be target developing combined immunotherapies.