In one decade, immunotherapy based on immune checkpoint blockades (ICBs) has become a new pillar of cancer treatment following surgery, radiation, chemotherapy, and targeted therapies. However, not all cancer patients benefit from single or combination therapy with anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies. Thus, an increasing number of immune checkpoint proteins (ICPs) have been screened and their effectiveness evaluated in preclinical and clinical trials. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain-containing-3 (TIM-3), and T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) constitute the second wave of immunotherapy targets that show great promise for use in the treatment of solid tumors and leukemia. To promote the research and clinical application of ICBs directed at these targets, we summarize their discovery, immunotherapy mechanism, preclinical efficiency, and clinical trial results in this review.

中文翻译：

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靶向 LAG-3、TIM-3 和 TIGIT 进行癌症免疫治疗

十年来，基于免疫检查点阻断（ICB）的免疫疗法已成为继手术、放疗、化疗和靶向治疗之后癌症治疗的新支柱。然而，并非所有癌症患者都受益于抗 CTLA-4 和抗 PD-1/PD-L1 单克隆抗体的单一或联合治疗。因此，越来越多的免疫检查点蛋白（ICP）被筛选出来，并在临床前和临床试验中评估其有效性。淋巴细胞激活基因 3 (LAG-3)、T 细胞免疫球蛋白和含粘蛋白结构域 3 (TIM-3) 以及具有免疫球蛋白和基于酪氨酸的抑制基序 (ITIM) 结构域 (TIGIT) 的 T 细胞免疫受体 (TIGIT) 构成第二个一波免疫治疗靶标在实体瘤和白血病的治疗中显示出巨大的应用前景。为了促进针对这些靶点的ICB的研究和临床应用，我们在这篇综述中总结了它们的发现、免疫治疗机制、临床前效率和临床试验结果。