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

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  • Marine Leclerc

    (INSERM UMR 1186, Gustave Roussy, EPHE, PSL, Faculté de Médecine-Université Paris-Sud, Université Paris-Saclay)

  • Elodie Voilin

    (INSERM UMR 1186, Gustave Roussy, EPHE, PSL, Faculté de Médecine-Université Paris-Sud, Université Paris-Saclay)

  • Gwendoline Gros

    (INSERM UMR 1186, Gustave Roussy, EPHE, PSL, Faculté de Médecine-Université Paris-Sud, Université Paris-Saclay)

  • Stéphanie Corgnac

    (INSERM UMR 1186, Gustave Roussy, EPHE, PSL, Faculté de Médecine-Université Paris-Sud, Université Paris-Saclay)

  • Vincent Montpréville

    (INSERM UMR 1186, Gustave Roussy, EPHE, PSL, Faculté de Médecine-Université Paris-Sud, Université Paris-Saclay
    Centre chirurgical Marie-Lannelongue, Service d’Anatomie Pathologie)

  • Pierre Validire

    (Institut Mutualiste Montsouris, Service d’Anatomie pathologique)

  • Georges Bismuth

    (INSERM U1016, Institut Cochin
    CNRS, Unité mixte de Recherche 8104
    Université Paris Descartes, Sorbonne Paris Cité)

  • Fathia Mami-Chouaib

    (INSERM UMR 1186, Gustave Roussy, EPHE, PSL, Faculté de Médecine-Université Paris-Sud, Université Paris-Saclay)

Abstract

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

Suggested Citation

  • Marine Leclerc & Elodie Voilin & Gwendoline Gros & Stéphanie Corgnac & Vincent Montpréville & Pierre Validire & Georges Bismuth & Fathia Mami-Chouaib, 2019. "Regulation of antitumour CD8 T-cell immunity and checkpoint blockade immunotherapy by Neuropilin-1," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11280-z
    DOI: 10.1038/s41467-019-11280-z
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    Cited by:

    1. Mike B. Barnkob & Yale S. Michaels & Violaine André & Philip S. Macklin & Uzi Gileadi & Salvatore Valvo & Margarida Rei & Corinna Kulicke & Ji-Li Chen & Vitul Jain & Victoria K. Woodcock & Huw Colin-Y, 2024. "Semaphorin 3A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Shilpa Bhatia & Diemmy Nguyen & Laurel B. Darragh & Benjamin Van Court & Jaspreet Sharma & Michael W. Knitz & Miles Piper & Sanjana Bukkapatnam & Jacob Gadwa & Thomas E. Bickett & Shiv Bhuvane & Sophi, 2022. "EphB4 and ephrinB2 act in opposition in the head and neck tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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