Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment.
Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment.
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DOI：
10.3892/ijo.2016.3785
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发表时间：
2017-01
影响因子：
5.2
通讯作者：
Kawashiri S
中科院分区：
文献类型：
--
作者：
Hirai M;Kitahara H;Kobayashi Y;Kato K;Bou-Gharios G;Nakamura H;Kawashiri S
阻断程序性死亡1受体（PD-1）/程序性死亡配体（PD-L1）通路可有效降低肿瘤生长并提高生存率。在最近的临床研究中，已经证明了阻断PD-1/PD-L1检查点可以实现持久的肿瘤消退。口腔鳞状细胞癌（OSCC）具有高度免疫抑制性，PD-L1表达已被认为是导致这种表型的潜在机制。尽管抗PD-1治疗可以产生持久的反应，但这种治疗似乎仅使一部分患者受益。因此，了解PD-L1在口腔鳞癌微环境中的表达调控机制是非常重要的。在这项研究中，我们发现PD-L1在高级别浸润性OSCC细胞系中的表达低于低级别浸润性OSCC细胞系，并发现PD-L1表达与上皮-间质转化（EMT）密切相关。PD-L1表达在高级别侵袭性人OSCC组织中的巨噬细胞和树突状细胞（DC）中上调，或与间充质表型OSCC细胞体外共培养。TLR 4抑制肽成功地抑制了与间充质表型OSCC细胞共培养的巨噬细胞和DC上的PD-L1上调，这表明一些EMT诱导的肿瘤抗原对于肿瘤相关巨噬细胞和DC上的PD-L1诱导至关重要。有必要进一步研究EMT对肿瘤免疫微环境的影响，并确定潜在的生物标志物，以选择可能优先受益于PD-1/PD-L1阻断或更广泛的免疫治疗的患者。
Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients. Thus, it is important to understand the mechanisms underlying regulation of PD-L1 expression in the OSCC microenvironment. In this study, we showed that PD-L1 expression in high-grade invasive OSCC cell lines was lower than that in a low-grade invasive OSCC line and found a close correlation between PD-L1 expression and the epithelial-mesenchymal transition (EMT). PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in vitro. TLR4-inhibitory peptide successfully suppressed PD-L1 upregulation on macrophages and DCs co-cultured with mesenchymal-phenotype OSCC cells, suggesting that some EMT-induced tumour antigen is critical for PD-L1 induction on tumour-associated macrophages and DCs. Further studies are necessary to explore the impact of EMT on the tumour immune microenvironment and to identify potential biomarkers for selecting patients who might preferentially benefit from PD-1/PD-L1 blockade or immunotherapies more broadly.
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口腔鳞状细胞癌中表皮生长因子受体表达的丧失与侵袭性和上皮间质转化有关。
影响因子：
2.9
作者：
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影响因子：
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