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TIM-3 shows multiple immunosuppressive effects across immune cell types and, through its stage-dependent expression in the tumor microenvironment, can reflect T cell exhaustion alongside PD-1. Combining TIM-3 blockade with PD-1/PD-L1 inhibition is being tested clinically. The review details TIM-3 and PD-1 biology, the TIM-3–PD-1/PD-L1 mechanisms driving immune evasion, and summarizes current trial status and anti-TIM-3 and anti-PD-1 antibodies.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/tim-3-teams-up-with-pd-1-in-cancer-immunotherapy-mechanisms-and-perspectives/372346/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/tim-3-teams-up-with-pd-1-in-cancer-immunotherapy-mechanisms-and-perspectives/372346.png","ImageObject",300,407,{"name":42,"@type":43},"Connor ","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why are immune checkpoint inhibitors not universally effective in cancer treatment?","Question",{"text":63,"@type":64},"Although ICIs have improved cancer therapy, the clinical response rate remains suboptimal. Some cancers exhibit resistance, motivating the search for additional targets and combination strategies.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What role does TIM-3 play in the tumor microenvironment and T cell exhaustion?",{"text":68,"@type":64},"TIM-3 has multiple immunosuppressive effects across immune cell types. Its differential expression during T cell dysfunction in the tumor microenvironment, together with PD-1, indicates T cell exhaustion.",{"name":70,"@type":61,"acceptedAnswer":71},"How does combining anti-TIM-3 with anti-PD-1/PD-L1 treatments aim to improve outcomes?",{"text":72,"@type":64},"The review proposes inhibiting TIM-3 together with PD-1 and PD-L1 to increase immunotherapy effectiveness. 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Molecular Biomedicine (2025) 6:27 [https://doi.org/10.1186/s43556-025-00267-6](https://doi.org/10.1186/s43556-025-00267-6)  \nMolecular Biomedicine  \n REVIEW Open Access  \nTIM-3 teams up with PD-1 in cancer  \nimmunotherapy: mechanisms and perspectives  \nZhuohong Yan1, Chunmao Wang2, JinghongWu1, Jinghui Wang1 and Teng Ma 1*  \nAbstract  \nImmunotherapy 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 ofT cell dysfunction in the tumor microenvironment (TME), TIM-3, along with programmed cell death protein 1 (PD-1), serves as indicators ofT 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.  \nKeywords Immune checkpoint inhibitors, TIM-3, PD-1/PD-L1, Immunotherapy, Combined therapy, Clinical trials  \nIntroduction  \nCancer treatment has witnessed the rise of a crucial approach-immunotherapy, making significant progress in the field. The identification and targeting of immune checkpoint molecules address the limitations of traditional treatments. Both stimulatory and inhibitory molecules are essential for maintaining the delicate immune system’s balance [1]. Immune checkpoint inhibitors (ICIs)  \n*Correspondence:  \nTeng Ma[mateng82913@163.com](mateng82913@163.com)  \n1 Department of Cancer Research Center, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China  \n2 Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China  \nhave successfully transferred from experimental research to clinical application, demonstrating promising efficacy in treating specific cancers. Ipilimumab, the first ICI that targets cytotoxic T lymphocyte antigen 4 (CTLA4), was authorized by the Food and Drug Administration (FDA) in 2011. FDA subsequently approved inhibitors targeting programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), and lymphocyte activation gene 3 (LAG-3). However, despite these significant advancements, the clinical response rate to ICIs remains suboptimal.  \nInhibitory immune checkpoint molecules, including PD-1, CTLA4, LAG-3, T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM)  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you g","cbCaivEc7Axn1xNC","https://ap.wps.com/l/cbCaivEc7Axn1xNC","pdf",2221667,24,"English","# Introduction\n## Immune checkpoint inhibitors and clinical limitations\n## Immune checkpoint molecule balance\n## TIM-3 as an inhibitory checkpoint in cancer immunotherapy\n## TIM-3 regulation, resistance links, and immune evasion mechanisms","[{\"question\":\"Why are immune checkpoint inhibitors not universally effective in cancer treatment?\",\"answer\":\"Although ICIs have improved cancer therapy, the clinical response rate remains suboptimal. Some cancers exhibit resistance, motivating the search for additional targets and combination strategies.\"},{\"question\":\"What role does TIM-3 play in the tumor microenvironment and T cell exhaustion?\",\"answer\":\"TIM-3 has multiple immunosuppressive effects across immune cell types. Its differential expression during T cell dysfunction in the tumor microenvironment, together with PD-1, indicates T cell exhaustion.\"},{\"question\":\"How does combining anti-TIM-3 with anti-PD-1/PD-L1 treatments aim to improve outcomes?\",\"answer\":\"The review proposes inhibiting TIM-3 together with PD-1 and PD-L1 to increase immunotherapy effectiveness. The combined strategy is being evaluated in ongoing clinical trials across multiple cancer types.\"}]","TIM-3 teams up with PD-1 in cancer immunotherapy - mechanisms and perspectives | PDF",1790194299]