食管癌干细胞来源的外泌体 O-GlcNAc 转移酶通过上调 CD8 T 细胞 PD-1 促进肿瘤免疫抑制。
Exosomal O-GlcNAc transferase from esophageal carcinoma stem cell promotes cancer immunosuppression through up-regulation of PD-1 in CD8 T cells.
机构信息
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
出版信息
Cancer Lett. 2021 Mar 1;500:98-106. doi: 10.1016/j.canlet.2020.12.012. Epub 2020 Dec 8.
Esophageal carcinoma stem cells (ECSCs) are responsible for the initiation and therapy-resistance of esophageal cancer. Nutrient sensor O-GlcNAc transferase (OGT) promoted the growth and metastasis of cancer cells. However, the contributions of OGT to the tumorigenesis of ECSCs remain largely uncover. In the present study, as compared to matched non-stem cancer cells, the expression of OGT was higher in ALDH ECSCs. Knock down of OGT by lentivirus system reduced the self-renewal capacities and tumorigenicity of ALDH ECSCs. In addition, OGT in exosome derived from ALDH ECSCs was taken up by neighboring CD8 T cells and increased the expression of PD-1 in CD8 T cells. Down-regulation of OGT increased the apoptosis of ALDH ECSCs induced by CD8 T cells, which could be blocked by overexpression of PD-1 in CD8 T cells. Together, OGT in exosome from ECSCs protects ECSCs from CD8 T cells through up-regulation of PD-1.
食管癌细胞干细胞（ECSCs）负责食管癌的起始和治疗耐药性。营养传感器 O-连接的 N-乙酰葡糖胺转移酶（OGT）促进了癌细胞的生长和转移。然而，OGT 对 ECSCs 肿瘤发生的贡献在很大程度上仍未被揭示。在本研究中，与匹配的非干细胞癌细胞相比，ALDH ECSCs 中的 OGT 表达更高。通过慢病毒系统敲低 OGT 可降低 ALDH ECSCs 的自我更新能力和致瘤性。此外，ALDH ECSCs 来源的外泌体中的 OGT 被邻近的 CD8 T 细胞摄取，并增加了 CD8 T 细胞中 PD-1 的表达。OGT 的下调增加了 CD8 T 细胞诱导的 ALDH ECSCs 的凋亡，而 CD8 T 细胞中 PD-1 的过表达可阻断这种作用。总之，ECSCs 来源的外泌体中的 OGT 通过上调 PD-1 来保护 ECSCs 免受 CD8 T 细胞的攻击。
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