细胞程式死亡-配体1
细胞程式死亡-配体1(英语:Programmed cell death 1 ligand 1,PD-L1)也称为表面抗原分化簇274(cluster of differentiation 274,CD274)或B7同源体1(B7 homolog 1,B7-H1),是人类体内的一种蛋白质,由CD274基因编码。[6]
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PD-L1是大小为40k道尔顿的第一型跨膜蛋白,据信其在某些特殊情形(例如怀孕、组织移植、自体免疫疾病,以及诸如肝炎等某些疾病)下,免疫系统的抑制有关。正常情形下免疫系统会对聚集在淋巴结或脾脏的外来抗原产生反应,促发具抗原特异性的细胞毒性T细胞(CD8+ T细胞)增殖。而细胞程式死亡受体-1(PD-1)与细胞程式死亡-配体1(PD-L1)结合,可以传导抑制性的信号,减低淋巴结CD8+ T细胞的增生, 而且PD-1还可以借由调节Bcl-2基因,控制淋巴结中抗原特异性T细胞的聚积。[7]
目前发现PD-L1表现的增加可能使癌症逃避宿主免疫系统。在来自肾细胞癌患者的196份肿瘤标本进行的分析发现,PD-L1的表现增加与肿瘤侵袭性增加和死亡风险增加4.5倍有关[8]。目前许多PD-L1抑制剂正在作为免疫肿瘤疗法发展中,并在临床试验中显示出良好的效果[9]。临床上可用的例子包括Durvalumab,atezolizumab和avelumab。[10]在正常组织中,STAT3和NF-κB等转录因子之间的反馈会限制免疫反应,从而保护宿主组织并限制发炎症状。在癌症中,转录因子之间反馈限制的丧失会导致局部PD-L1表达增加,这可能会限制针对PD-L1药物的全身治疗有效性。[11]
参考资料
编辑- ^ 對細胞程式死亡-配體1起作用的藥物;在維基數據上查看/編輯參考.
- ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000120217 - Ensembl, May 2017
- ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000016496 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Entrez Gene: CD274 CD274 molecule.
- ^ Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. Journal of Immunology. July 2004, 173 (2): 945–54. PMID 15240681.
- ^ Dranoff, Glenn. Faculty of 1000 evaluation for Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target.. F1000 - Post-publication peer review of the biomedical literature. 2004-12-09 [2019-12-21].
- ^ Association Between Clinicopathological Features and Programmed Death Ligand 1 Expression in Non-small Cell Lung Cancer. Anticancer Research. 2018-01-20, 38 (2). ISSN 0250-7005. doi:10.21873/anticanres.12326.
- ^ American Cancer Society | Information and Resources about for Cancer: Breast, Colon, Lung, Prostate, Skin. www.cancer.org. [2019-12-21]. (原始内容存档于2018-08-03) (英语).
- ^ Spiros, A. Vlahopoulos. Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode. Cancer Biology & Medicine. 2017, 14 (3): 254. ISSN 2095-3941. doi:10.20892/j.issn.2095-3941.2017.0029.