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Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells.


ABSTRACT: The role of invariant natural killer T (iNKT) cells in antitumor immunity has been studied extensively, and clinical trials in patients with advanced cancer have revealed a prolonged survival in some cases. In recent years, humanized blocking antibodies against co-stimulatory molecules such as PD-1 have been developed. The enhancement of T cell function is reported to improve antitumor immunity, leading to positive clinical effects. However, there are limited data on the role of PD-1/programmed death ligand (PDL) molecules in human iNKT cells. In this study, we investigated the interaction between PD-1 on iNKT cells and PDL on antigen-presenting cells (APCs) in the context of iNKT cell stimulation. The blockade of PDL1 at the time of stimulation resulted in increased release of helper T cell (Th) 1 cytokines from iNKT cells, leading to the activation of NK cells. The direct antitumor function of iNKT cells was also enhanced after stimulation with anti-PDL1 antibody-treated APCs. According to these results, we conclude that the co-administration of anti-PDL1 antibody and alpha-galactosylceramide (?GalCer)-pulsed APCs enhances iNKT cell-mediated antitumor immunity.

SUBMITTER: Kamata T 

PROVIDER: S-EPMC5099366 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells.

Kamata Toshiko T   Suzuki Akane A   Mise Naoko N   Ihara Fumie F   Takami Mariko M   Makita Yuji Y   Horinaka Atsushi A   Harada Kazuaki K   Kunii Naoki N   Yoshida Shigetoshi S   Yoshino Ichiro I   Nakayama Toshinori T   Motohashi Shinichiro S  

Cancer immunology, immunotherapy : CII 20160915 12


The role of invariant natural killer T (iNKT) cells in antitumor immunity has been studied extensively, and clinical trials in patients with advanced cancer have revealed a prolonged survival in some cases. In recent years, humanized blocking antibodies against co-stimulatory molecules such as PD-1 have been developed. The enhancement of T cell function is reported to improve antitumor immunity, leading to positive clinical effects. However, there are limited data on the role of PD-1/programmed  ...[more]

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