Down‐regulation of EOMES drives T‐cell exhaustion via abolishing EOMES‐mediated repression of inhibitory receptors of T cells in liver cancer
| العنوان: | Down‐regulation of EOMES drives T‐cell exhaustion via abolishing EOMES‐mediated repression of inhibitory receptors of T cells in liver cancer |
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| المؤلفون: | Yong Yi, Yi-Peng Fu, Jia-Xing Wang, Hong-Wei He, Shuang-Jian Qiu, Xiao-Yan Cai, Xiao-Chun Ni |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Carcinoma, Hepatocellular, genetic structures, T-Lymphocytes, T cell, T cells, Receptors, Antigen, T-Cell, Down-Regulation, Eomesodermin, Kaplan-Meier Estimate, CD8-Positive T-Lymphocytes, Biology, medicine.disease_cause, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Downregulation and upregulation, medicine, Humans, PD‐1/CTAL‐4, Transcription factor, Psychological repression, Neoplasm Staging, Liver Neoplasms, Cancer, Original Articles, hepatocellular carcinoma, Cell Biology, Middle Aged, Immune Checkpoint Proteins, Prognosis, medicine.disease, eye diseases, Gene Expression Regulation, Neoplastic, inhibitory receptors, 030104 developmental biology, medicine.anatomical_structure, eomesodermin, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, Original Article, Female, sense organs, T-Box Domain Proteins, Carcinogenesis, CD8 |
| الوصف: | T‐cell exhaustion is one of the hallmarks in cancer, but the mechanisms underlying T‐cell dysregulation remains unclear. Here, we reported that down‐regulation of transcription factor EOMES contributed to increased levels of inhibitory receptors in T cell among the tumour tissues and resulted in the poor prognosis of hepatocellular carcinoma (HCC). By analysing the correlation between EOMES in tumour‐infiltrating T cells and the clinical features, we demonstrated that the EOMES was related to the advanced stage and poor prognosis of HCC. Further mechanistic studies revealed that the EOMES mainly expressed in the CD8+ T cells and were down‐regulated in tumour samples. Moreover, we demonstrated that the EOMES directly bound at the transcriptional regulatory regions of the key inhibitory factors including PD‐1, CTAL‐4 and CD39, and lower levels of EOMES contributed to overexpression of these factors in T cells. Together, our studies provide new insight into the transcriptional deregulation of the inhibitory receptors on T cells during the tumorigenesis. |
| تدمد: | 1582-4934 1582-1838 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3163a5feb667d4baa5523ce6359163a0 https://doi.org/10.1111/jcmm.15898 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3163a5feb667d4baa5523ce6359163a0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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