[Objective]To investigate the induction of exhausted T cell generation by adenosine and its impact on the migration and apoptosis of renal clear cell carcinoma cells.[Methods]Flow cytometry was employed to assess the expression of CD8+T cells and the exhaustion marker TIM-3 in renal clear cell carcinoma and adjacent tissues.Bioinformatics analysis was conducted to identify genes that influence T cell exhaustion in renal clear cell carcinoma and adjacent tissues.Stable knockdown of the gene was achieved in renal clear cell carcinoma 786-O cells using shRNA technology,and the cellular behaviors including migration and apoptosis were assessed.Various tumor-conditioned media were prepared to culture CD8+T cells and investigate the impact of gene knockout in renal clear cell carcinoma cells on exhausted T cells.[Results]Renal clear cell carcinoma exhibited elevated expression levels of CD8+T cells and TIM-3 in comparison to adjacent tissues.Bioinformatics analysis revealed increased expression of adenosine synthesis rate-limiting enzyme NT5E(CD73)in renal clear cell carcinoma.Clinical specimens exhibited higher expression levels of adenosine and CD73 in renal clear cell carcinoma tissues when compared to adjacent tissues.Knockout of NT5E in 786-O cells led to reduced migration ability and enhanced apoptosis compared to the control group.CD8+T cells cultured in tumor-conditioned media with NT5E knockout exhibited diminished expression of programmed death protein 1 and decreased proliferation capacity.[Conclusion]Renal clear cell carcinoma tissues display exhausted CD8+T cells and elevated expression of adenosine and CD73.Knockout of NT5E in renal clear cell carcinoma 786-O cells diminishes migration ability and enhances apoptosis.Knockout of NT5E can decrease adenosine synthesis and attenuate the generation of exhausted T cells.
关键词
肾透明细胞癌/腺苷/耗竭型CD8+T细胞/NT5E(CD73)/CD8+T细胞/肿瘤微环境
Key words
renal clear cell carcinoma/adenosine/exhausted T lymphocytes/NT5E(CD73)/CD8+T cells/tumor microenvironment
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