Project description:To determine the transcriptomic differences between CT-26 and Colon 26, we sequenced RNA from these cell lines as well as tumors isolated ex vivo from tumor bearing animals at sizes 100, 400 and 800 mm3
Project description:Cancer 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.
Project description:modENCODE_submission_3068 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP500(official name : OP500 genotype : unc119(ed3);wgIs500(ceh-26::TY1 EGFP FLAG;unc119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Dresden using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The CEH-26::EGFP fusion protein is expressed in the correct ceh-26 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the CEH-26 transcription factor. made_by : R. Waterston ); Developmental Stage: late embryo; Genotype: unc119(ed3);wgIs500(ceh-26::TY1 EGFP FLAG;unc119); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage late embryo; Target gene ceh-26; Strain OP500(official name : OP500 genotype : unc119(ed3);wgIs500(ceh-26::TY1 EGFP FLAG;unc119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Dresden using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The CEH-26::EGFP fusion protein is expressed in the correct ceh-26 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the CEH-26 transcription factor. made_by : R. Waterston ); temp (temperature) 20 degree celsius