National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
Sci Rep. 2016 Aug 3;6:30923. doi: 10.1038/srep30923.
T lymphocyte-mediated immune responses are critical for antitumour immunity; however, T cell function is impaired in the tumour environment. MicroRNAs are involved in regulation of the immune system. While little is known about the function of intrinsic microRNAs in CD8(+) T cells in the tumour microenvironment. Here, we found that miR-491 was upregulated in CD8(+) T cells from mice with colorectal cancer. Retroviral overexpression of miR-491 in CD8(+) and CD4(+) T cells inhibited cell proliferation and promoted cell apoptosis and decreased the production of interferon-γ in CD8(+) T cells. We found that miR-491 directly targeted cyclin-dependent kinase 4, the transcription factor T cell factor 1 and the anti-apoptotic protein B-cell lymphoma 2-like 1 in CD8(+) T cells. Furthermore, tumour-derived TGF-β induced miR-491 expression in CD8(+) T cells. Taken together, our results suggest that miR-491 can act as a negative regulator of T lymphocytes, especially CD8(+) T cells, in the tumour environment; thus, this study provides a novel insight on dysfunctional CD8(+) T cells during tumourigenesis and cancer progression. In conclusion, miR-491 may be a new target for antitumour immunotherapy.
T 淋巴细胞介导的免疫应答对于抗肿瘤免疫至关重要;然而,T 细胞在肿瘤微环境中的功能受到损害。微小 RNA 参与免疫系统的调节。虽然关于肿瘤微环境中 CD8(+)T 细胞中内在微小 RNA 的功能知之甚少。在这里,我们发现 miR-491 在结直肠癌小鼠的 CD8(+)T 细胞中上调。miR-491 在 CD8(+)和 CD4(+)T 细胞中的逆转录病毒过表达抑制细胞增殖,促进细胞凋亡,并减少 CD8(+)T 细胞中干扰素-γ的产生。我们发现 miR-491 直接靶向 CD8(+)T 细胞中的细胞周期蛋白依赖性激酶 4、转录因子 T 细胞因子 1 和抗凋亡蛋白 B 细胞淋巴瘤 2 样 1。此外,肿瘤衍生的 TGF-β 诱导 CD8(+)T 细胞中 miR-491 的表达。总之,我们的研究结果表明,miR-491 可作为肿瘤微环境中 T 淋巴细胞(尤其是 CD8(+)T 细胞)的负调节剂;因此,本研究为肿瘤发生和癌症进展过程中功能失调的 CD8(+)T 细胞提供了新的见解。综上所述,miR-491 可能是抗肿瘤免疫治疗的新靶点。