GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334984/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334984GEOGSEfalseIL-26-driven epigenetic remodelling promotes immune evasion in colorectal cancerCancer cells acquire malignant traits through epigenetic remodeling driven by exposure to inflammatory secretomes within the tumor microenvironment. However, how immune-derived inflammatory factors regulate cancer cell epigenetics remains poorly understood. Here, we show that IL-26 produced by tumor-specific type 17 T cells acts as a key mediator that induces epigenetic reprogramming associated with cancer malignancy. We identify a selective accumulation of IL-26–expressing T cells in tumors resistant to immune checkpoint blockade therapy in colorectal cancer. Notably, IL-26 functioned as a noncanonical cytokine by translocating into the nucleus of tumor cells, where it directly bound the transcription factor STAT1 and formed transcriptional complexes with NF-κB and AP-1. Nuclear IL-26 further induced a transcriptionally active chromatin state characterized by enrichment of BRD4 and H3K27ac, resulting in robust upregulation of CXCL chemokines. This process promoted excessive neutrophil infiltration and enhanced immune evasion and tumor progression through suppression of CD8+ T cell responses. Together, these findings support a conceptual model in which tumor-specific type 17 T cells directly reprogram cancer cell epigenetics through IL-26, thereby reshaping the tumor immune microenvironment to promote immune evasion.2026/06/19GSE334984GSM9802966GSM9802965GSM9802964GSM9802963GSM9802973GSM9802962GSM9802972GSM9802971GSM9802970GSM9802969GSM9802968GSM980296734284334984Homo sapiens