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

Sep 24, 2026

T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) expression is discussed as a trending immune checkpoint marker across diverse neoplasms, highlighting its differential expression and relevance to cancer prognosis. TIM-3 is presented as a key receptor interacting with GAL-9, PtdSer, HMGB1 and CEACAM1, regulating immune responses from Th1 and cytotoxic lymphocytes to monocytes, macrophages, NK cells, and dendritic cells. The article reviews TIM-3’s prognostic potential and the impact of coexpressed checkpoint inhibitors, and summarizes clinical trials using TIM-3 targeting monoclonal, bispecific, and cell-based therapies.

LanguageEnglish

CategoryHealthcare

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Pages21

Reading Time53 min

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Abstract

TIM‑3 structure and function

TIM‑3 ligands and immune regulatory effects

Cancer Immunology, Immunotherapy (2023) 72:3405–3425 [https://doi.org/10.1007/s00262-023-03516-1](https://doi.org/10.1007/s00262-023-03516-1) TIM‑3 as a promising target for cancer immunotherapy in a wide range of tumors Natalia Sauer1 · Natalia Janicka1 · Wojciech Szlasa2 · Bartłomiej Skinderowicz3 · Katarzyna Kołodzińska3 · Wioletta Dwernicka4 · Małgorzata Oślizło2 · Julita Kulbacka5,6 · Vitalij Novickij5,7 · Katarzyna Karłowicz‑Bodalska8 Received: 30 June 2023 / Accepted: 2 August 2023 / Published online: 11 August 2023 © The Author(s) 2023 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 monoclonaland bispecific antibodies in monotherapy and combination therapy and highlighted the emerging role of cell-based therapies. Keywords Cancer · Immunotherapy · TIM-3 · T-cells * Julita Kulbacka [julita.kulbacka@umw.edu.pl](julita.kulbacka@umw.edu.pl) 1 Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland 2 Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland 3 Faculty of Chemistry, Wroclaw University of Science and Technology, Wroclaw, Poland 4 Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland 5 State Research Institute Centre for Innovative Medicine, Department of Immunology, Vilnius, Lithuania 6 Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland 7 Faculty of Electronics, Vilnius Gediminas Technical University, Vilnius, Lithuania 8 Department of Drug Technology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland TIM‑3 structure and function T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is identified as an immune checkpoint that is expressed in various kinds of immune cells and plays a key role in immunoregulation. TIM-3 belongs to the TIM family, which includes three members in humans (TIM-1, TIM-3 and TIM-4) and eight members in mice (TIM-1 to TIM-8) . Members of the TIM family are type I surface glycoproteins that share similar molecular structures containing a mucin domain, amino-terminal immunoglobulin variable domain (V domain) with five noncanonical cysteines, a transmembrane domain and a cytoplasmic tail [1, 2] . The IgV Tim-3 domain is formed of antiparallel beta sheets. A disulfide bond formed by four non-canonical cysteines binds the front and back sheets together to stabilize the IgV domain [3] . These two bonds form a unique"cleft" in Tim-3 and a small associated channel. The cleft formed by the CC′ and FG loops is stabilized by two noncanonical disulfide bonds, as well as a series of conserved ionic interactions and hydrogen bonds. It is a response site for ligand binding, such as phosphatidylserine. These unique conformational surface features may be involved in Tim-3's biological function of ligand recognition [4] . The IgV domain is stabilized by two hydrogen bonds, which are present in almost all IgSF domains—

FAQs

What is TIM-3 and why is it important in cancer immunotherapy?

TIM-3 is an immune checkpoint receptor expressed across multiple immune cell types. Its interactions with ligands and its differential expression across tumors make it relevant to cancer prognosis and treatment strategies.

Which ligands interact with TIM-3 and what do they influence?

TIM-3 interacts with GAL-9, PtdSer, HMGB1 and CEACAM1. These interactions activate biochemical pathways that contribute to immune tolerance and suppression of certain T-cell responses.

How do coexpressed immune checkpoints relate to patient outcomes?

The article discusses how coexpressed immune checkpoint inhibitors such as LAG-3, PD-1, and CTLA-4 can influence patients’ outcomes when TIM-3 is involved.

Sep 24, 2026

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