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探索免疫检查点抑制剂:聚焦于PD-1/PD-L1轴及其他方面。

Exploring immune checkpoint inhibitors: Focus on PD-1/PD-L1 axis and beyond.

作者信息

Aden Durre, Zaheer Samreen, Sureka Niti, Trisal Monal, Chaurasia Jai Kumar, Zaheer Sufian

机构信息

Department of Pathology, Hamdard Institute of Medical science and research, Jamia Hamdard, New Delhi, India.

Department of Radiotherapy, Jawaharlal Nehru Medical College, AMU, Aligarh, India.

出版信息

Pathol Res Pract. 2025 May;269:155864. doi: 10.1016/j.prp.2025.155864. Epub 2025 Mar 1.

Abstract

Immunotherapy emerges as a promising approach, marked by recent substantial progress in elucidating how the host immune response impacts tumor development and its sensitivity to various treatments. Immune checkpoint inhibitors have revolutionized cancer therapy by unleashing the power of the immune system to recognize and eradicate tumor cells. Among these, inhibitors targeting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have garnered significant attention due to their remarkable clinical efficacy across various malignancies. This review delves into the mechanisms of action, clinical applications, and emerging therapeutic strategies surrounding PD-1/PD-L1 blockade. We explore the intricate interactions between PD-1/PD-L1 and other immune checkpoints, shedding light on combinatorial approaches to enhance treatment outcomes and overcome resistance mechanisms. Furthermore, we discuss the expanding landscape of immune checkpoint inhibitors beyond PD-1/PD-L1, including novel targets such as CTLA-4, LAG-3, TIM-3, and TIGIT. Through a comprehensive analysis of preclinical and clinical studies, we highlight the promise and challenges of immune checkpoint blockade in cancer immunotherapy, paving the way for future advancements in the field.

摘要

免疫疗法成为一种很有前景的方法,其标志是最近在阐明宿主免疫反应如何影响肿瘤发展及其对各种治疗的敏感性方面取得了重大进展。免疫检查点抑制剂通过释放免疫系统识别和根除肿瘤细胞的能力,彻底改变了癌症治疗。其中,靶向程序性细胞死亡蛋白1(PD-1)及其配体(PD-L1)的抑制剂因其在各种恶性肿瘤中的显著临床疗效而备受关注。本综述深入探讨了围绕PD-1/PD-L1阻断的作用机制、临床应用和新兴治疗策略。我们探索了PD-1/PD-L1与其他免疫检查点之间的复杂相互作用,阐明了增强治疗效果和克服耐药机制的联合方法。此外,我们还讨论了除PD-1/PD-L1之外免疫检查点抑制剂不断扩展的领域,包括CTLA-4、LAG-3、TIM-3和TIGIT等新靶点。通过对临床前和临床研究的全面分析,我们突出了癌症免疫治疗中免疫检查点阻断的前景和挑战,为该领域的未来进展铺平了道路。

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