MiR-29 enables immune evasion of colon cancer by regulating fucosylation-mediated Ras-GTP signal in CD8+ T cells

Immune checkpoint blockade (ICB) therapies such as PD-1 antibodies has shown remarkable clinical success in the control of tumor growth, yet only a fraction of patients benefits from such therapy. As a result, there is increasing interest in boosting the effectiveness of ICB by combining it with other treatments. Objectives: Screening critical microRNAs that inhibit colon tumor growth in concert with ICB based on the effectiveness of immunotherapy and the gene expression levels in colorectal patients and revealing the regulatory mechanism. Overall design: We analyzed microRNAs, which are upregulated in colorectal patients, negatively correlated with immune score, and responsive to anti-PD-1 therapy using R language. Next, mice with conditional disruption of miR-29ab1 specifically in the intestinal epithelium were administered azoxymethane and dextran sodium sulfate to induce tumor formation. Furthermore, immune status in the tumor microenvironment was evaluated by flow cytometry immunofluorescence. Transcriptomics and metabolomics were performed to study the underlying mechanisms. We performed protein extraction and purification and luciferase assays to study genes and proteins that miR-29ab1 regulated in CD8+ T cells or CTLL-2 cells. Tissues were obtained, and histology and immunohistochemistry were used for analysis.