SOX10 Inhibits T Cell Recognition by Inducing Expression of the Immune Checkpoint Molecule PD-L1 in A375 Melanoma Cells
SOX10 Inhibits T Cell Recognition by Inducing Expression of the Immune Checkpoint Molecule PD-L1 in A375 Melanoma Cells
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DOI：
10.21873/anticanres.16296
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发表时间：
2023-04-01
影响因子：
2
通讯作者：
Torigoe, Toshihiko
中科院分区：
文献类型：
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作者：
Sasaki, Kenta;Hirohashi, Yoshihiko;Torigoe, Toshihiko
背景/目的：恶性黑色素瘤是一种致命的皮肤癌，是表达黑色素瘤分化抗原和新抗原的免疫原性最强的恶性肿瘤之一。SRY相关HMG盒10（SOX 10）是一种转录因子和神经嵴分化标志物，用作黑色素瘤的诊断标志物，同时通过激活SOX 10-MITF轴在黑色素瘤起始中发挥作用。SOX 10显示通过诱导免疫检查点分子（例如，HVEM和CEACAM 1）。在这项研究中，我们旨在研究SOX 10与免疫检查点分子程序性死亡-1配体1（PD-L1）表达之间的关系。材料与方法：使用SOX 10基因转染和SOX 10 siRNA转染到A375黑素瘤细胞中进行SOX 10过表达和敲低。通过流式细胞术和蛋白质印迹法评估PD-L1表达。T细胞应答使用NY-ESO-1特异性TCR转导的T（TCR-T）细胞通过IFN？ELISP 0 T测定。结果：SOX 10过表达增加PD-L1的表达，而使用siRNA敲低SOX 10则降低其表达。干扰素？ELISPOT分析显示，SOX 10的过表达降低了细胞对NY-ESO-1特异性TCR-T细胞的敏感性。结论：SOX 10通过表达PD-L1参与黑色素瘤的内在免疫抑制机制。
Background/Aim: Malignant melanoma is a fatal skin cancer and is among the most immunogenic malignancies expressing melanoma-differentiation antigens and neoantigens. SRY-related HMG-box 10 (SOX10) is a transcription factor and a neural-crest differentiation marker that is used as a diagnostic marker for melanoma whilst playing a role in melanoma initiation through activation of the SOX10-MITF axis. SOX10 was shown to play a role in melanoma initiation by inducing expression of immune checkpoint molecules (e.g., HVEM and CEACAM1). In this study, we aimed to investigate the relationship between SOX10 and the expression an immune checkpoint molecule, programmed death-1 ligand 1 (PD-L1). Materials and Methods: SOX10 overexpression and knockdown was performed using SOX10 gene transfection and SOX10 siRNA transfection into A375 melanoma cells. PD-L1 expression was assessed by flow cytometry and western blotting. T cell response was evaluated using NY-ESO-1 specific TCR-transduced T (TCR-T) cells by IFN? ELISPOT assay. Results: SOX10 overexpression increased the expression of PD-L1, whereas SOX10 knockdown, using siRNA, decreased its expression. IFN? ELISPOT assay revealed that overexpression of SOX10 decreased the susceptibility of cells to NY-ESO-1-specific TCR-T cells. Conclusion: SOX10 has a role in the intrinsic immune suppressive mechanisms of melanoma through expression of PD-L1.