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TIM-3 作为一种有前途的靶点,可用于多种肿瘤的癌症免疫治疗。

TIM-3 as a promising target for cancer immunotherapy in a wide range of tumors.

机构信息

Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland.

Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland.

出版信息

Cancer Immunol Immunother. 2023 Nov;72(11):3405-3425. doi: 10.1007/s00262-023-03516-1. Epub 2023 Aug 11.

Abstract

T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) expression has been a trending topic in recent years due to its differential expression in a wide range of neoplasms. TIM-3 is one of the key immune checkpoint receptors that interact with GAL-9, PtdSer, HMGB1 and CEACAM1. Initially identified on the surface of T helper 1 (Th1) lymphocytes and later on cytotoxic lymphocytes (CTLs), monocytes, macrophages, natural killer cells (NKs), and dendritic cells (DCs), TIM-3 plays a key role in immunoregulation. Recently, a growing body of evidence has shown that its differential expression in various tumor types indicates a specific prognosis for cancer patients. Here, we discuss which types of cancer TIM-3 can serve as a prognostic factor and the influence of coexpressed immune checkpoint inhibitors, such as LAG-3, PD-1, and CTLA-4 on patients' outcomes. Currently, experimental medicine involving TIM-3 has significantly enhanced the anti-tumor effect and improved patient survival. In this work, we summarized clinical trials incorporating TIM-3 targeting monoclonal and bispecific antibodies in monotherapy and combination therapy and highlighted the emerging role of cell-based therapies.

摘要

T 细胞免疫球蛋白和黏蛋白结构域蛋白 3(TIM-3)的表达近年来成为研究热点,这是由于其在广泛的肿瘤中存在差异表达。TIM-3 是与 GAL-9、PtdSer、HMGB1 和 CEACAM1 相互作用的关键免疫检查点受体之一。TIM-3 最初在辅助性 T 细胞 1(Th1)淋巴细胞和后来的细胞毒性 T 淋巴细胞(CTL)、单核细胞、巨噬细胞、自然杀伤细胞(NK)和树突状细胞(DC)表面被鉴定出来,在免疫调节中发挥关键作用。最近,越来越多的证据表明,其在各种肿瘤类型中的差异表达表明癌症患者具有特定的预后。在这里,我们讨论了 TIM-3 可以作为哪种类型癌症的预后因素,以及共表达的免疫检查点抑制剂(如 LAG-3、PD-1 和 CTLA-4)对患者预后的影响。目前,涉及 TIM-3 的实验医学显著增强了抗肿瘤作用并提高了患者的生存率。在这项工作中,我们总结了 TIM-3 靶向单克隆和双特异性抗体在单药和联合治疗中的临床试验,并强调了基于细胞的治疗方法的新作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c3/10992306/01bd203949b0/262_2023_3516_Fig1_HTML.jpg

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