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

被引：54

作者：

Kamata, Toshiko ^{[1
,2
]}

Suzuki, Akane ^{[1
]}

Mise, Naoko ^{[1
]}

Ihara, Fumie ^{[1
]}

Takami, Mariko ^{[1
]}

Makita, Yuji ^{[1
,3
]}

Horinaka, Atsushi ^{[3
]}

Harada, Kazuaki ^{[1
]}

Kunii, Naoki ^{[3
]}

Yoshida, Shigetoshi ^{[2
]}

Yoshino, Ichiro ^{[2
]}

Nakayama, Toshinori ^{[4
]}

Motohashi, Shinichiro ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Med Immunol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan

[2] Chiba Univ, Grad Sch Med, Dept Gen Thorac Surg, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan

[3] Chiba Univ, Grad Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan

[4] Chiba Univ, Grad Sch Med, Dept Immunol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan

来源：

CANCER IMMUNOLOGY IMMUNOTHERAPY | 2016年 / 65卷 / 12期

关键词：

Invariant NKT cells; Anti-PDL1; antibody; PD-1; Antitumor immunity; NKT CELLS; TUMOR-IMMUNOTHERAPY; CANCER; PD-1; SYSTEM; CYTOTOXICITY; ACTIVATION; INDUCTION; INFECTION; ANTIBODY;

D O I：

10.1007/s00262-016-1901-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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 (alpha GalCer)-pulsed APCs enhances iNKT cell-mediated antitumor immunity.

引用

页码：1477 / 1489

页数：13

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