期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 65, 期 12, 页码 1477-1489出版社
SPRINGER
DOI: 10.1007/s00262-016-1901-y
关键词
Invariant NKT cells; Anti-PDL1 antibody; PD-1; Antitumor immunity
资金
- Ministry of Education, Culture, Sports, Science and Technology (Japan) [24592083, 26861119]
- Ministry of Health, Labour and Welfare
- Grants-in-Aid for Scientific Research [15K20181, 24592083, 16K19974, 26861119] Funding Source: KAKEN
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.
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