Targeting inhibitory immune checkpoint molecules has dramatically changed treatment paradigms in medical oncology. Understanding the best strategies to unleash a pre-existing immune response or to induce an efficient immune response against tumors has emerged as a research priority. In this work, we focus on a novel target for cancer immunotherapy, the inhibitory receptor T-cell immunoglobulin and mucin domain 3 (TIM3). This narrative review describes TIM3 biology in different (tumor-infiltrating) immune cells, particularly in the immunosuppressive regulatory T cells and dysfunctional/exhausted cytotoxic T lymphocytes, but also in cells that confer innate immunity - natural killer and dendritic cells. We discuss the functional role of TIM3, its expression and its clinical significance in a variety of tumors, and confront the heterogeneous results emerging from different studies, including clinical trials of immunotherapy. Finally, this work summarizes the principal early-phase clinical trials exploring TIM3 blockade and discusses some future perspectives.

中文翻译：

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TIM3表达在癌症中的意义：从生物学到临床。

靶向抑制性免疫检查点分子已极大地改变了医学肿瘤学的治疗范例。研究最佳方法以释放预先存在的免疫反应或诱导针对肿瘤的有效免疫反应已成为研究的重点。在这项工作中，我们专注于癌症免疫治疗的新靶标，即抑制性受体T细胞免疫球蛋白和粘蛋白结构域3（TIM3）。这篇叙述性综述描述了不同免疫（肿瘤浸润）免疫细胞中的TIM3生物学，尤其是免疫抑制性调节性T细胞和功能异常/疲惫的细胞毒性T淋巴细胞，以及赋予先天免疫力的细胞-自然杀伤细胞和树突状细胞。我们讨论了TIM3在多种肿瘤中的功能作用，其表达及其临床意义，并面对来自不同研究（包括免疫疗法的临床试验）的异类结果。最后，这项工作总结了探索TIM3阻断的主要早期临床试验，并讨论了一些未来的观点。