PD-L1在恶性肿瘤中的重要性全面了解PD-L1在恶性肿瘤中的作用:从分子机制到治疗机会。

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Mojdeh Soltani, Mohammad Abbaszadeh, Hamed Fouladseresht, Mark J M Sullman, Nahid Eskandari
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引用次数: 0

摘要

程序性死亡配体1 (PD-L1)表达上调的现象在许多人类恶性肿瘤中很常见。PD-L1的过度表达明显有助于免疫逃避,因为它与活化T淋巴细胞上的PD-1受体的相互作用通过中和T细胞刺激信号而损害抗肿瘤免疫。此外,除了其免疫界面,PD-L1还具有直接调节致癌过程的内在能力,促进癌细胞的增殖和存活。PD-L1的这种双重功能挑战了免疫检查点抑制剂的功效,并突出了其作为治疗直接靶点的可能应用。最近关于PD-L1的癌细胞内在信号通路的发现大大增强了我们对其肿瘤特异性表达的病理意义的理解。这些包括肿瘤增殖和生存的协调,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。本综述旨在提供详尽的PD-L1的分子基础合成及其在一系列癌症中的临床意义,包括实体肿瘤和血液系统疾病。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的综合理解的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities.

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.

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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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