Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells.
Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells.
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DOI：
10.1007/s00262-016-1901-y
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发表时间：
2016-12
影响因子：
5.8
通讯作者：
Motohashi, Shinichiro
中科院分区：
文献类型：
--
作者：
Kamata, Toshiko;Suzuki, Akane;Mise, Naoko;Ihara, Fumie;Takami, Mariko;Makita, Yuji;Horinaka, Atsushi;Harada, Kazuaki;Kunii, Naoki;Yoshida, Shigetoshi;Yoshino, Ichiro;Nakayama, Toshinori;Motohashi, Shinichiro
不变性自然杀伤T细胞（iNKT）在抗肿瘤免疫中的作用已被广泛研究，在晚期癌症患者的临床试验中发现，在某些情况下，iNKT细胞可以延长生存期。近年来，针对PD-1等共刺激分子的人源化阻断抗体已被开发出来。据报道，T细胞功能的增强可以提高抗肿瘤免疫，从而产生积极的临床效果。然而，关于PD-1/程序性死亡配体（PDL）分子在人iNKT细胞中的作用的数据有限。在这项研究中，我们研究了在iNKT细胞刺激的情况下，iNKT细胞上的PD-1和抗原呈递细胞（APCs）上的PDL之间的相互作用。刺激时PDL1的阻断导致iNKT细胞中辅助性T细胞（Th） 1细胞因子的释放增加，导致NK细胞的活化。经抗pdl1抗体处理的apc刺激后，iNKT细胞的直接抗肿瘤功能也增强。根据这些结果，我们得出结论，抗pdl1抗体和α -半乳糖神经酰胺（αGalCer）脉冲apc共同给药可增强iNKT细胞介导的抗肿瘤免疫。本文的在线版本（doi:10.1007/s00262-016-1901-y）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1007/s00262-016-1901-y) contains supplementary material, which is available to authorized users.
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DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
3.1
作者：
Kee, Seung-Jung;Kwon, Yong-Soo;Ryang, Dong-Wook
通讯作者：
Ryang, Dong-Wook
DOI：
10.4049/jimmunol.0803648
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Parekh VV;Lalani S;Kim S;Halder R;Azuma M;Yagita H;Kumar V;Wu L;Kaer LV
通讯作者：
Kaer LV
影响因子：
6.4
作者：
Ishikawa, E;Motohashi, S;Nakayama, T
通讯作者：
Nakayama, T
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM