IL-26-driven epigenetic remodelling promotes immune evasion in colorectal cancer

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.