細胞程式死亡-配體1
細胞程式死亡-配體1(英語:Programmed cell death 1 ligand 1,PD-L1)也稱為表面抗原分化簇274(cluster of differentiation 274,CD274)或B7同源體1(B7 homolog 1,B7-H1),是人類體內的一種蛋白質,由CD274基因編碼。[6]
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PD-L1是大小為40k道爾頓的第一型跨膜蛋白,據信其在某些特殊情形(例如懷孕、組織移植、自體免疫疾病,以及諸如肝炎等某些疾病)下,免疫系統的抑制有關。正常情形下免疫系統會對聚集在淋巴結或脾臟的外來抗原產生反應,促發具抗原特異性的細胞毒性T細胞(CD8+ T細胞)增殖。而細胞程式死亡受體-1(PD-1)與細胞程式死亡-配體1(PD-L1)結合,可以傳導抑制性的信號,減低淋巴結CD8+ T細胞的增生, 而且PD-1還可以藉由調節Bcl-2基因,控制淋巴結中抗原特異性T細胞的聚積。[7]
目前發現PD-L1表現的增加可能使癌症逃避宿主免疫系統。在來自腎細胞癌患者的196份腫瘤標本進行的分析發現,PD-L1的表現增加與腫瘤侵襲性增加和死亡風險增加4.5倍有關[8]。目前許多PD-L1抑製劑正在作為免疫腫瘤療法發展中,並在臨床試驗中顯示出良好的效果[9]。臨床上可用的例子包括Durvalumab,atezolizumab和avelumab。[10]在正常組織中,STAT3和NF-κB等轉錄因子之間的反饋會限制免疫反應,從而保護宿主組織並限制發發炎狀。在癌症中,轉錄因子之間反饋限制的喪失會導致局部PD-L1表達增加,這可能會限制針對PD-L1藥物的全身治療有效性。[11]
參考資料
- ^ 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]. (原始內容存檔於2018-08-03) (英語).
- ^ 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.