CD8 + T Cells in Gastrointestinal Cancer: a Perspective on Targeting MicroRNA.

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.