Unleashing the Power of immune Checkpoints: A new strategy for enhancing Treg cells depletion to boost antitumor immunity

IF 5.6 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-02-06 Epub Date: 2025-01-06 DOI:10.1016/j.intimp.2024.113952

Guoxin Li , Siqi Li , Yilin Jiang , Tao Chen , Zhengwen An

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Abstract

Regulatory T (Treg) cells, immunosuppressive CD4⁺ T cells, can impede anti-tumor immunity, complicating cancer treatment. Since their discovery, numerous studies have been dedicated to understand Treg cell biology, with a focus on checkpoint pathways’ role in their generation and function. Immune checkpoints, such as PD-1/PD-L1, CTLA-4, TIGIT, TIM-3, and OX40, are pivotal in controlling Treg cell expansion and activity in the tumor microenvironment (TME), affecting their ability to suppress immune responses. This review examines the complex relationship between these checkpoints and Tregs in the TME, and how they influence tumor immunity. We also discuss the therapeutic potential of targeting these checkpoints to enhance anti-tumor immunity, including the use of immune checkpoint blockade (ICB) therapies and novel approaches such as CCR8-targeted therapies. Understanding the interaction between immune checkpoints and Treg cells can lead to more effective immunotherapeutic strategies, such as combining CCR8-targeted therapies with immune checkpoint inhibitors, to improve patient outcomes in cancer treatment.

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释放免疫检查点的力量：增强Treg细胞消耗以增强抗肿瘤免疫的新策略。

调节性T （Treg）细胞，免疫抑制性CD4+ T细胞，可阻碍抗肿瘤免疫，使癌症治疗复杂化。自从他们的发现以来，许多研究都致力于了解Treg细胞生物学，重点关注检查点通路在其产生和功能中的作用。免疫检查点，如PD-1/PD-L1、CTLA-4、TIGIT、TIM-3和OX40，在控制Treg细胞在肿瘤微环境（TME）中的扩增和活性，影响其抑制免疫反应的能力方面起着关键作用。本文综述了TME中这些检查点与Tregs之间的复杂关系，以及它们如何影响肿瘤免疫。我们还讨论了靶向这些检查点以增强抗肿瘤免疫的治疗潜力，包括使用免疫检查点阻断（ICB）疗法和新方法，如ccr8靶向治疗。了解免疫检查点和Treg细胞之间的相互作用可以带来更有效的免疫治疗策略，例如将ccr8靶向治疗与免疫检查点抑制剂相结合，以改善癌症治疗患者的预后。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.