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抑制 CRNDE 通过调控 miR-545-5p 和 TIM-3 增强 CD8+T 细胞对口腔鳞状细胞癌的抗肿瘤活性。

Repression of CRNDE enhances the anti-tumour activity of CD8 + T cells against oral squamous cell carcinoma through regulating miR-545-5p and TIM-3.

机构信息

School of Stomatology and Medicine, Foshan Stomatological Hospital, Foshan University, Foshan, China.

Department of Prosthodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China.

出版信息

J Cell Mol Med. 2021 Dec;25(23):10857-10868. doi: 10.1111/jcmm.16909. Epub 2021 Nov 2.

Abstract

Immunotherapy has been identified a promising treatment of cancers, including Oral squamous cell carcinoma (OSCC). CRNDE is highly overexpressed in various cancers. Many lncRNAs have been reported in CD8 T lymphocytes. Little is investigated about their effects in the functions of CD8 + T cells in OSCC. Currently, the influence of lncRNA CRNDE on the function of CD8 + T cells in OSCC progression was investigated. Here, CRNDE was obviously elevated and negatively correlated with IFN-γ production in tumour-infiltrating CD8 + T cells isolated from OSCC patients. CRNDE can exhibit a crucial role in activating CD8 + T-cell exhaustion. Mechanistically, CRNDE specifically sponged miR-545-5p to induce T-cell immunoglobulin and mucin domain-3 (TIM-3), thus contributing to CD8 + T-cell exhaustion. The function of miR-545-5p on T-cell function remains poorly known. TIM-3 is a significant immune checkpoint, and it inhibits cancer immunity. TIM-3 can demonstrate an important role in CD8 + T-cell exhaustion. In summary, loss of CRNDE could induce miR-545-5p and inhibit TIM3 expression, thus significantly activated the anti-tumour effect of CD8 + T cells.

摘要

免疫疗法已被确定为癌症的一种有前途的治疗方法,包括口腔鳞状细胞癌(OSCC)。CRNDE 在各种癌症中高度过表达。许多 lncRNA 已在 CD8+T 淋巴细胞中报道。关于它们在 OSCC 中 CD8+T 细胞功能中的作用的研究很少。目前,研究了 lncRNA CRNDE 对 OSCC 进展中 CD8+T 细胞功能的影响。在这里,CRNDE 在肿瘤浸润性 CD8+T 细胞中明显升高,并与 IFN-γ 的产生呈负相关,这些细胞是从 OSCC 患者中分离出来的。CRNDE 可以在激活 CD8+T 细胞衰竭中发挥关键作用。从机制上讲,CRNDE 特异性地吸附 miR-545-5p 以诱导 T 细胞免疫球蛋白和粘蛋白域 3(TIM-3),从而导致 CD8+T 细胞衰竭。miR-545-5p 对 T 细胞功能的功能仍然知之甚少。TIM-3 是一个重要的免疫检查点,它抑制癌症免疫。TIM-3 在 CD8+T 细胞衰竭中可以发挥重要作用。总之,CRNDE 的缺失可以诱导 miR-545-5p 的表达并抑制 TIM3 的表达,从而显著激活 CD8+T 细胞的抗肿瘤作用。

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