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PD-L1在恶性肿瘤中的重要性:对PD-L1在恶性肿瘤中作用的全面见解,从分子机制到治疗机遇

PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities.

作者信息

Soltani Mojdeh, Abbaszadeh Mohammad, Fouladseresht Hamed, Sullman Mark J M, Eskandari Nahid

机构信息

Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus.

出版信息

Clin Exp Med. 2025 Apr 3;25(1):106. doi: 10.1007/s10238-025-01641-y.

Abstract

The phenomenon of upregulated programmed death-ligand 1 (PD-L1) expression is common in numerous human malignancies. The overexpression of PD-L1 significantly contributes to immune evasion because its interaction with the PD-1 receptor on activated T lymphocytes impairs anti-tumour immunity by neutralizing T cell stimulatory signals. Furthermore, beyond its immunological interface, PD-L1 possesses intrinsic capabilities that directly modulate oncogenic processes, fostering cancer cell proliferation and survival. This dual function of PD-L1 challenges the efficacy of immune checkpoint inhibitors and highlights its possible application as a direct target for therapy. Recent discoveries concerning the cancer cell-intrinsic signalling pathways of PD-L1 have significantly enhanced our understanding of the pathological implications linked to its tumour-specific expression. These entail the orchestration of tumour proliferation and viability, maintenance of cancer stem cell-like phenotypes, modulation of immune responses, as well as impacts on DNA repair mechanisms and transcriptional regulation. This review aims to deliver an exhaustive synthesis of PD-L1's molecular underpinnings alongside its clinical implications in a spectrum of cancers, spanning both solid neoplasms and haematological disorders. It underscores the necessity for an integrated understanding of PD-L1 in further refining therapeutic strategies and improving patient outcomes.

摘要

程序性死亡配体1(PD-L1)表达上调的现象在众多人类恶性肿瘤中很常见。PD-L1的过表达显著促进免疫逃逸,因为它与活化T淋巴细胞上的PD-1受体相互作用,通过中和T细胞刺激信号来损害抗肿瘤免疫。此外,除了其免疫界面外,PD-L1还具有直接调节致癌过程、促进癌细胞增殖和存活的内在能力。PD-L1的这种双重功能挑战了免疫检查点抑制剂的疗效,并突出了其作为直接治疗靶点的可能应用。最近关于PD-L1癌细胞内在信号通路的发现显著增强了我们对与其肿瘤特异性表达相关的病理意义的理解。这些包括肿瘤增殖和活力的调控、癌症干细胞样表型的维持、免疫反应的调节,以及对DNA修复机制和转录调控的影响。这篇综述旨在全面综合PD-L1的分子基础及其在一系列癌症(包括实体肿瘤和血液系统疾病)中的临床意义。它强调了在进一步完善治疗策略和改善患者预后方面对PD-L1进行综合理解的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a19/11968484/33a6b4b7438d/10238_2025_1641_Fig1_HTML.jpg

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