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


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.

SUBMITTER: Leclerc M 

PROVIDER: S-EPMC6659631 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Leclerc Marine M   Voilin Elodie E   Gros Gwendoline G   Corgnac Stéphanie S   de Montpréville Vincent V   Validire Pierre P   Bismuth Georges G   Mami-Chouaib Fathia F  

Nature communications 20190726 1


Neuropilin-1 (Nrp-1) is a marker for murine CD4<sup>+</sup>FoxP3<sup>+</sup> regulatory T (Treg) cells, a subset of human CD4<sup>+</sup> Treg cells, and a population of CD8<sup>+</sup> 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<sup>+</sup> T cells displaying PD-1<sup>hi</sup> status and infiltrating human lung cancer. Interaction of Nrp-1 with its ligand semap  ...[more]

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