Department of Medical and Molecular Biology, Medical University of Silesia, Faculty of Medical Sciences in Zabrze, Poland.
Department of Medical and Molecular Biology, Medical University of Silesia, Faculty of Medical Sciences in Zabrze, Poland.
Exp Mol Pathol. 2020 Oct;116:104494. doi: 10.1016/j.yexmp.2020.104494. Epub 2020 Jul 15.
The maintenance of homeostasis of the immune system depends on the balance between excitatory and inhibitory signals. Programmed death ligand (PD-L1) is a molecule which downregulates the immune system targeting the programmed death receptor 1 (PD-1). Under physiological conditions, the receptor is constitutively expressed in lymphocytes. The PD-L1 / PD-1 pathway plays a key role in completing the immune response in the right way, preventing excessive stimulation of the cells of the immune system, protecting the organism against autoimmunity. Under pathological conditions PD-L1 expression may take place in tumor cells. Binding of PD-1 to its ligand on tumor cells suppresses T lymphocytes through a negative feedback. This mechanism allows abnormal cells to avoid destruction by the host immune system. The expression of PD-L1 in tumors has been described in many histological types of cancer: melanoma, lung cancer, breast and ovarian, pancreatic and esophagus adenocarcinoma, kidney tumors and bladder cancers as well as in hematopoietic malignancies. Many studies report a significant effect of PD-L1 polymorphisms on clinical parameters of patients. Studies of PD-L1 polymorphisms showed their influence on the stage of cancer, effectiveness of chemotherapy and prognosis after tumor resection. Further analysis of the polymorphisms may result in development of effective therapies that restore anti-tumor immunity. Inhibition of PD-L1 / PD-1 is one of the most promising immunotherapies for various types of cancer. This work was intended to present information about the impact of PD-L1 gene expression and polymorphisms on the clinical parameters of patients with cancer.
免疫系统的内稳态维持依赖于兴奋和抑制信号之间的平衡。程序性死亡配体 1（PD-L1）是一种下调免疫系统的分子，其靶点是程序性死亡受体 1（PD-1）。在生理条件下，该受体在淋巴细胞中持续表达。PD-L1/PD-1 通路在正确完成免疫反应中起着关键作用，防止免疫系统细胞过度刺激，保护机体免受自身免疫。在病理条件下，PD-L1 可在肿瘤细胞中表达。PD-1 与其在肿瘤细胞上配体的结合通过负反馈抑制 T 淋巴细胞。该机制使异常细胞逃避宿主免疫系统的破坏。PD-L1 在肿瘤中的表达已在许多组织学类型的癌症中描述：黑色素瘤、肺癌、乳腺和卵巢癌、胰腺癌和食管腺癌、肾肿瘤和膀胱癌以及血液系统恶性肿瘤。许多研究报告 PD-L1 多态性对患者临床参数有显著影响。PD-L1 多态性的研究表明其对癌症分期、化疗效果和肿瘤切除后的预后有影响。对多态性的进一步分析可能导致开发出恢复抗肿瘤免疫的有效疗法。PD-L1/PD-1 的抑制是各种类型癌症最有前途的免疫疗法之一。这项工作旨在介绍 PD-L1 基因表达和多态性对癌症患者临床参数的影响信息。
