Department of Pediatric Surgery, The General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Department of General Surgery, Wuzhong People's Hospital Affiliated to Ningxia Medical University, Wuzhong, 751100, Ningxia, China.
Funct Integr Genomics. 2023 Sep 30;23(4):312. doi: 10.1007/s10142-023-01231-9.
Recent advances in immunotherapeutic approaches have the potential to bring new hope to the treatment of pancreatic cancer. The tumor microenvironment contributes significantly to tumor development and progression. In this study, miR-429 overexpression was found to inhibit proliferation, invasion, and clonogenicity while promoting apoptosis in HepG2 cells. Furthermore, co-culture of miR-429-overpressing or silenced HepG2 cells with PBMCs showed that miR-429 induced CD4+ and CD8+ T cell infiltration, decreased the numbers of Tregs, inhibited CD8+ T cell apoptosis and exhaustion, and enhanced CD8+ T cell functions in PBMCs. miR-429 was found to prevent an immunosuppressive HCC microenvironment by targeting and suppressing PD-L1. In a C57BL/6 mouse subcutaneous xenograft tumor model, overexpression of miR-429 reduced tumorigenesis and both tumor volumes and weights were decreased relative to controls. In addition, CD4+ and CD8+ T cells were increased, Tregs were reduced, and CD8+ T cell apoptosis and depletion were reduced in the tumor tissues induced by miR-429-overexpressing HepG2 cells.
最近在免疫治疗方法方面的进展有可能给胰腺癌的治疗带来新的希望。肿瘤微环境对肿瘤的发展和进展有重大贡献。在这项研究中，发现 miR-429 的过表达抑制了 HepG2 细胞的增殖、侵袭和克隆形成，同时促进了细胞凋亡。此外，miR-429 过表达或沉默的 HepG2 细胞与 PBMCs 的共培养表明，miR-429 诱导 CD4+和 CD8+T 细胞浸润，减少 Tregs 的数量，抑制 CD8+T 细胞凋亡和耗竭，并增强 PBMCs 中 CD8+T 细胞的功能。miR-429 通过靶向和抑制 PD-L1 来防止免疫抑制性 HCC 微环境。在 C57BL/6 小鼠皮下异种移植肿瘤模型中，miR-429 的过表达减少了肿瘤的发生，与对照组相比，肿瘤体积和重量均降低。此外，miR-429 过表达的 HepG2 细胞诱导的肿瘤组织中 CD4+和 CD8+T 细胞增加，Tregs 减少，CD8+T 细胞凋亡和耗竭减少。
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