title: 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 (αGalCer)-pulsed APCs enhances iNKT cell-mediated antitumor immunity.
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.|Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Kamata
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Mise
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Ihara
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Takami
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.|Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Makita
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Horinaka
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Harada
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kunii
authors.affiliation: Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. motohashi@faculty.chiba-u.jp.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D008024:Ligands; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology* / Q000378:metabolism
chemical_list: D008024:Ligands; D061026:Programmed Cell Death 1 Receptor
keywords: Anti-PDL1 antibody; Antitumor immunity; Invariant NKT cells; PD-1