PD-L1 promotes head and neck squamous cell carcinoma cell growth through mTOR signaling
PD-L1 promotes head and neck squamous cell carcinoma cell growth through mTOR signaling
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PD-L1通过mTOR信号促进头颈鳞状细胞癌细胞生长
DOI：
10.3892/or.2019.7053
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发表时间：
2019-03
期刊：
影响因子：
4.2
通讯作者：
Tao Zezhang
中科院分区：
文献类型：
--
作者：
Zheng Anyuan;Li Fen;Chen Fuhai;Zuo Jingjing;Wang Lei;Wang Yongping;Chen Shiming;Xiao Bokui;Tao Zezhang
程序性死亡配体1（PD-L1）是一种免疫共刺激分子，表达于各种癌细胞和免疫细胞表面。其在肿瘤细胞上的过表达抑制免疫应答，促进肿瘤细胞免疫逃逸。目前的研究表明，PD-L1在头颈部鳞状细胞癌（HNSCC）的癌变过程中至关重要。HNSCC组织微阵列的免疫组化分析显示，PD-L1在肿瘤组织中过表达，并且随着肿瘤恶性程度的进展（从I级到IV级），其表达增加。随后，PD-L1的表达在HNSCC细胞系Cal-27和Fadu中被敲低或过表达。结果表明，PD-L1显著诱导HNSCC细胞增殖和集落形成能力。在Cal-27细胞异种移植BALB/c裸鼠中也促进细胞增殖。此外，通过蛋白质印迹法确定，PD-L1介导的HNSCC细胞增殖的增加可能与哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的激活有关。此外，mTOR抑制剂（雷帕霉素）阻止增殖的增加。基于这些结果，可以得出结论，PD-L1通过mTOR信号传导促进HNSCC细胞的细胞增殖，并且阻断PD-L1可能有助于HNSCC治疗。
Programmed death-ligand 1 (PD-L1), an immune co-stimulatory molecule, is expressed on various cancer cells and the surface of immune cells. Its overexpression on tumor cells suppresses the immune response to promote tumor cell immune escape. The present study demonstrated that PD-L1 was critical in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. Immunohistochemical analysis of HNSCC tissue microarrays revealed that PD-L1 was overexpressed in tumor tissue, and its expression increased as tumor malignancy progressed (from grade I to IV). Subsequently, the expression of PD-L1 was knocked down or overexpressed in the HNSCC cell lines Cal-27 and Fadu. It was demonstrated that PD-L1 significantly induced HNSCC cell proliferation and colony forming ability. Cell proliferation was also promoted in Cal-27 cell xenograft BALB/c nude mice. In addition, it was determined by western blotting that the PD-L1-mediated increase in HNSCC cell proliferation may have been associated with the activation of mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, mTOR inhibitor (rapamycin) prevented the increase in proliferation. Based on these results, it was concluded that PD-L1 promoted cell proliferation of HNSCC cells through mTOR signaling, and blocking PD-L1 may be conducive in HNSCC therapy.
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影响因子：
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