Targeting novel inhibitory receptors in cancer immunotherapy.
Targeting novel inhibitory receptors in cancer immunotherapy.
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DOI：
10.1016/j.smim.2020.101436
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发表时间：
2020-06
影响因子：
7.8
通讯作者：
Zarour HM
中科院分区：
文献类型：
--
作者：
Ding QQ;Chauvin JM;Zarour HM
T细胞在促进实验模型和人类的肿瘤消退中起着关键作用。然而，在癌症进展期间长期暴露于肿瘤抗原的T细胞可能变得功能失调/耗尽，并且不能诱导肿瘤破坏。这种肿瘤诱导的T细胞功能障碍可能通过多种机制发生。特别是，在许多癌症中由肿瘤浸润淋巴细胞上调的免疫检查点抑制性受体限制了T细胞的存活和功能。克服这种抑制性受体介导的T细胞功能障碍一直是癌症免疫治疗最近发展的中心焦点。靶向抑制性受体途径（如程序性细胞死亡1（PD-1）/程序性死亡配体1和细胞毒性T淋巴细胞相关抗原4（CTLA-4））的免疫疗法，单独或联合使用，在多种肿瘤类型中具有显著的临床获益。然而，许多癌症患者对免疫检查点阻断没有反应，PD-1/CTLA-4双重阻断可能会导致严重的不良事件，这限制了其适应症。靶向导致肿瘤微环境中肿瘤诱导的T细胞功能障碍的新型非冗余抑制性受体途径可能被证明是有效且无毒的。本文综述了T细胞免疫球蛋白和粘蛋白结构域3（TIM-3）和含IG和ITIM结构域的T细胞免疫受体（TIGIT）/CD 226/CD 96/CD 112 R在肿瘤免疫治疗中的作用。
T cells play a critical role in promoting tumor regression in both experimental models and humans. Yet, T cells that are chronically exposed to tumor antigen during cancer progression can become dysfunctional/exhausted and fail to induce tumor destruction. Such tumor-induced T cell dysfunction may occur via multiple mechanisms. In particular, immune checkpoint inhibitory receptors that are upregulated by tumor-infiltrating lymphocytes in many cancers limit T cell survival and function. Overcoming this inhibitory receptor-mediated T cell dysfunction has been a central focus of recent developments in cancer immunotherapy. Immunotherapies targeting inhibitory receptor pathways such as programmed cell death 1 (PD-1)/programmed death ligand 1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), alone or in combination, confer significant clinical benefits in multiple tumor types. However, many patients with cancer do not respond to immune checkpoint blockade, and dual PD-1/CTLA-4 blockade may cause serious adverse events, which limits its indications. Targeting novel non-redundant inhibitory receptor pathways contributing to tumor-induced T cell dysfunction in the tumor microenvironment may prove efficacious and non-toxic. This review presents preclinical and clinical findings supporting the roles of two key pathways—T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and T cell immunoreceptor with Ig and ITIM domain (TIGIT)/CD226/CD96/CD112R—in cancer immunotherapy.
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DOI：
10.4049/jimmunol.0903435
发表时间：
2010-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Boenisch O;D'Addio F;Watanabe T;Elyaman W;Magee CN;Yeung MY;Padera RF;Rodig SJ;Murayama T;Tanaka K;Yuan X;Ueno T;Jurisch A;Mfarrej B;Akiba H;Yagita H;Najafian N
通讯作者：
Najafian N
影响因子：
30.5
作者：
Chiba, Shigeki;Baghdadi, Muhammad;Akiba, Hisaya;Yoshiyama, Hironori;Kinoshita, Ichiro;Dosaka-Akita, Hirotoshi;Fujioka, Yoichiro;Ohba, Yusuke;Gorman, Jacob V.;Colgan, John D.;Hirashima, Mitsuomi;Uede, Toshimitsu;Takaoka, Akinori;Yagita, Hideo;Jinushi, Masahisa
通讯作者：
Jinushi, Masahisa
影响因子：
--
作者：
Bai, Jianwen;Li, Xiaoyan;Li, Qinchuan
通讯作者：
Li, Qinchuan
影响因子：
11.2
作者：
Carlsten, Mattias;Bjorkstrom, Niklas K.;Malmberg, Karl Johan
通讯作者：
Malmberg, Karl Johan
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John