Yuan Zihan, He Wei, Luo Wenjia, Huang Chunxia, Li Miao, You Jie, Wu Jiaqiang, Yang Kangping, Yang Liang
Department of Gastroenterological Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
The First Clinical Medical College of Nanchang University, Nanchang, 330006, China.
J Mol Med (Berl). 2025 Jul 17. doi: 10.1007/s00109-025-02574-5.
Gastrointestinal cancer, which is highly prevalent globally, constitutes a major threat to human health and life. The discovery of PD-L1/PD-1 has revolutionized immunotherapy, which has led to a shift in attention toward the antitumor functions of CD8 + T cells. CD8 + T cells are crucial effector cells in antitumor immunity, yet their functionality undergoes profound changes within the tumor microenvironment (TME). In the TME, gene mutations in cancer cells serve as initiating factors, remodeling the functions of various cells and the composition of noncellular substances. Cancer cells induce functional changes in other cells within the TME to favor their survival, notably impacting crucial antitumor effector cells such as CD8 + T cells, thereby furthering tumor progression. However, how tumor cells remodel CD8 + T cells remains inadequately understood, and targeted therapies against immune checkpoints face increasing challenges. An increasing number of findings suggest that miRNAs play a critical role in the process of remodeling CD8 + T cell function in tumors. Tumor cells regulate the expression of their own miRNAs to control the expression of surface molecules, modulate the release of secreted factors, or, through miRNA-containing exosomes, communicate with and remodel the function of CD8 + T cells. Elucidating the communication between CD8 + T cells and gastrointestinal cancer cells from a miRNA perspective to explain the shift of CD8 + T cells toward favorable types of tumors may inspire new therapeutic strategies. KEY MESSAGES: MicroRNAs regulate CD8+ T cells function in gastrointestinal cancers. MicroRNAs involve in crosstalk of gastrointestinal cancers with CD8+ T cells. MicroRNAs involve in crosstalk of the gastrointestinal immune microenvironment with CD8+ T cells. Focus on the application of targeted microRNA drugs and microRNA delivery strategies in gastrointestinal cancers.
胃肠道癌在全球范围内高度流行，对人类健康和生命构成重大威胁。PD-L1/PD-1的发现彻底改变了免疫疗法，使人们的注意力转向CD8 + T细胞的抗肿瘤功能。CD8 + T细胞是抗肿瘤免疫中的关键效应细胞，但其功能在肿瘤微环境（TME）中会发生深刻变化。在TME中，癌细胞中的基因突变作为起始因素，重塑各种细胞的功能和非细胞物质的组成。癌细胞诱导TME中其他细胞发生功能变化以利于其存活，尤其影响关键的抗肿瘤效应细胞如CD8 + T细胞，从而促进肿瘤进展。然而，肿瘤细胞如何重塑CD8 + T细胞仍未得到充分了解，针对免疫检查点的靶向治疗面临越来越多的挑战。越来越多的研究结果表明，miRNA在肿瘤中重塑CD8 + T细胞功能的过程中起关键作用。肿瘤细胞调节自身miRNA的表达以控制表面分子的表达、调节分泌因子的释放，或通过含miRNA的外泌体与CD8 + T细胞进行通讯并重塑其功能。从miRNA角度阐明CD8 + T细胞与胃肠道癌细胞之间的通讯，以解释CD8 + T细胞向有利肿瘤类型的转变，可能会激发新的治疗策略。关键信息：微小RNA调节胃肠道癌中CD8 + T细胞的功能。微小RNA参与胃肠道癌与CD8 + T细胞的相互作用。微小RNA参与胃肠道免疫微环境与CD8 + T细胞的相互作用。关注靶向微小RNA药物和微小RNA递送策略在胃肠道癌中的应用。
