TIM-3与PD-1在癌症免疫治疗中的合作:机制和观点

IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zhuohong Yan, Chunmao Wang, Jinghong Wu, Jinghui Wang, Teng Ma
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引用次数: 0

摘要

在过去的十年中,使用免疫检查点抑制剂(ICIs)进行免疫治疗已成为癌症治疗的重要策略。然而,ICIs的疗效仍然有限,某些癌症对这些治疗方法表现出耐药性。因此,几种免疫检查点蛋白目前正在临床前和临床研究中进行彻底筛选和评估。在这些候选者中,T细胞免疫球蛋白和粘蛋白结构域-3 (TIM-3)被认为是一个有希望的靶标。TIM-3对多种类型的免疫细胞具有多重免疫抑制作用。鉴于TIM-3在肿瘤微环境(TME)中T细胞功能障碍不同阶段的差异表达水平,TIM-3与程序性细胞死亡蛋白1 (PD-1)一起作为T细胞衰竭的指标。此外,仔细评估癌细胞中TIM-3和PD-1表达对免疫治疗效果的影响至关重要。为了提高抗TIM-3和抗PD-1治疗的有效性,建议联合抑制TIM-3、PD-1和程序性死亡配体1 (PD-L1)。TIM-3抑制与PD-1/PD-L1抑制剂联合使用的疗效正在许多正在进行的针对各种癌症患者的临床试验中进行评估。本研究系统探讨了TIM-3和PD-1的基础生物学,以及TIM-3和PD-1/PD-L1轴参与癌症免疫逃避的详细机制。此外,本文还全面分析了正在进行的临床试验,评估PD-1/PD-L1和TIM-3抑制剂在抗癌治疗中的协同作用,并概述了TIM-3和PD-1抗体的现状。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.

Immunotherapy using immune checkpoint inhibitors (ICIs) has become a prominent strategy for cancer treatment over the past ten years. However, the efficacy of ICIs remains limited, with certain cancers exhibiting resistance to these therapeutic approaches. Consequently, several immune checkpoint proteins are presently being thoroughly screened and assessed in both preclinical and clinical studies. Among these candidates, T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is considered a promising target. TIM-3 exhibits multiple immunosuppressive effects on various types of immune cells. Given its differential expression levels at distinct stages of T cell dysfunction in the tumor microenvironment (TME), TIM-3, along with programmed cell death protein 1 (PD-1), serves as indicators of T cell exhaustion. Moreover, it is crucial to carefully evaluate the impact of TIM-3 and PD-1 expression in cancer cells on the efficacy of immunotherapy. To increase the effectiveness of anti-TIM-3 and anti-PD-1 therapies, it is proposed to combine the inhibition of TIM-3, PD-1, and programmed death-ligand 1 (PD-L1). The efficacy of TIM-3 inhibition in conjunction with PD-1/PD-L1 inhibitors is being evaluated in a number of ongoing clinical trials for patients with various cancers. This study systematically investigates the fundamental biology of TIM-3 and PD-1, as well as the detailed mechanisms through which TIM-3 and PD-1/PD-L1 axis contribute to cancer immune evasion. Additionally, this article provides a thorough analysis of ongoing clinical trials evaluating the synergistic effects of combining PD-1/PD-L1 and TIM-3 inhibitors in anti-cancer treatment, along with an overview of the current status of TIM-3 and PD-1 antibodies.

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CiteScore
6.30
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