The TIM3/Gal9 signaling pathway: An emerging target for cancer immunotherapy.
The TIM3/Gal9 signaling pathway: An emerging target for cancer immunotherapy.
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DOI：
10.1016/j.canlet.2021.04.011
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发表时间：
2021-07-10
期刊：
影响因子：
9.7
通讯作者：
Cheng K
中科院分区：
文献类型：
--
作者：
Kandel S;Adhikary P;Li G;Cheng K
免疫检查点阻断在广泛的癌症中显示出前所未有的持久临床反应。T细胞免疫球蛋白和粘蛋白结构域3（TIM 3）是在肿瘤浸润淋巴细胞中高度表达的抑制性检查点蛋白。在各种癌症中，TIM 3和半乳糖凝集素9（Gal 9）的相互作用抑制由先天性以及适应性免疫细胞介导的抗肿瘤免疫。因此，阻断TIM 3/Gal 9相互作用是癌症治疗的有希望的治疗方法。此外，TIM 3/Gal 9途径沿着PD-1/PD-L1途径的共阻断通过克服由每个检查点诱导的非冗余免疫抗性来增加治疗功效。在这里，我们总结了TIM 3/Gal 9途径在适应性和先天免疫系统中的生理作用。我们强调了最近的临床和临床前研究，这些研究表明TIM 3/Gal 9通路参与了各种实体癌和血液癌。此外，我们讨论了使用TIM 3和Gal 9作为不同癌症的预后和预测生物标志物的潜力。对癌症中TIM 3/Gal 9信号通路阻断的深入机制理解可以帮助识别对这种疗法有反应的患者以及设计联合疗法。
Immune checkpoint blockade has shown unprecedented and durable clinical response in a wide range of cancers. T cell immunoglobulin and mucin domain 3 (TIM3) is an inhibitory checkpoint protein that is highly expressed in tumor-infiltrating lymphocytes. In various cancers, the interaction of TIM3 and Galectin 9 (Gal9) suppresses anti-tumor immunity mediated by innate as well as adaptive immune cells. Thus, the blockade of the TIM3/Gal9 interaction is a promising therapeutic approach for cancer therapy. In addition, co-blockade of the TIM3/Gal9 pathway along with the PD-1/PD-L1 pathway increases the therapeutic efficacy by overcoming non-redundant immune resistance induced by each checkpoint. Here, we summarize the physiological roles of the TIM3/Gal9 pathway in adaptive and innate immune systems. We highlight the recent clinical and preclinical studies showing the involvement of the TIM3/Gal9 pathway in various solid and blood cancers. In addition, we discuss the potential of using TIM3 and Gal9 as prognostic and predictive biomarkers in different cancers. An in-depth mechanistic understanding of the blockade of the TIM3/Gal9 signaling pathway in cancer could help in identifying patients who respond to this therapy as well as designing combination therapies.
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影响因子：
13.5
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