PDF(Pubmed)
Abstract：
Although inhibitors targeting the PD1/PD-L1 immune checkpoint are showing comparably good outcomes, a significant percentage of head and neck squamous cell carcinoma (HNSCC) patients do not respond to treatment. Apart from using different treatment strategies, another possibility would be to target other immune checkpoints operating in these non-responding tumors. To obtain an overview of which checkpoint ligands are expressed on HNSCC tumor cells and if these ligands are affected by HGF/MET signaling, we used mRNA sequencing and antibody-based techniques for identifying checkpoint ligands in six HNSCC tumor cell lines. Furthermore, we compared our results to mRNA sequencing data. From the checkpoint ligands we investigated, VISTA was expressed the highest at the RNA level and was also the most ubiquitously expressed. PD-L2 and B7-H3 were expressed comparably lower and were not present in all cell lines to the same extent. B7-H4, however, was only detectable in the Detroit 562 cell line. Concerning the effect of HGF on the ligand levels, PD-L2 expression was enhanced with HGF stimulation, whereas other checkpoint ligand levels decreased with stimulation. B7-H4 levels in the Detroit 562 cell line drastically decreased with HGF stimulation. This is of interest because both the checkpoint ligand and the growth factor are reported to be connected to epithelial-mesenchymal transition in the literature.
摘要：
尽管针对PD1/PD-L1免疫检查点的抑制剂显示出相当好的结果，相当比例的头颈部鳞状细胞癌(HNSCC)患者对治疗无反应.除了使用不同的治疗策略，另一种可能性是针对在这些无反应肿瘤中运行的其他免疫检查点。为了获得在HNSCC肿瘤细胞上表达哪些检查点配体的概述，如果这些配体受到HGF/MET信号的影响，我们使用mRNA测序和基于抗体的技术在6种HNSCC肿瘤细胞系中鉴定检查点配体.此外，我们将我们的结果与mRNA测序数据进行了比较.从我们调查的检查点配体来看，VISTA在RNA水平上表达最高,并且也是最普遍表达的。PD-L2和B7-H3的表达相对较低,并且在所有细胞系中不存在相同程度。然而，B7-H4，仅在底特律562细胞系中检测到。关于HGF对配体水平的影响，PD-L2表达随着HGF刺激而增强，而其他检查点配体水平随着刺激而降低。在HGF刺激下，底特律562细胞系中的B7-H4水平急剧下降。这是令人感兴趣的,因为在文献中都报道了检查点配体和生长因子与上皮-间质转化有关。
