E2F1-induced autocrine IL-6 inflammatory loop mediates cancer-immune crosstalk that predicts T cell phenotype switching and therapeutic responsiveness.

ABSTRACT: Melanoma is a metastatic, drug-refractory cancer with the ability to evade immunosurveillance. Cancer immune evasion involves interaction between tumor intrinsic properties and the microenvironment. The transcription factor E2F1 is a key driver of tumor evolution and metastasis. To explore E2F1's role in immune regulation in presence of aggressive melanoma cells, we established a coculture system and utilized transcriptome and cytokine arrays combined with bioinformatics and structural modeling. We identified an E2F1-dependent gene regulatory network with IL6 as a central hub. E2F1-induced IL-6 secretion unleashes an autocrine inflammatory feedback loop driving invasiveness and epithelial-to-mesenchymal transition. IL-6-activated STAT3 physically interacts with E2F1 and cooperatively enhan

SUBMITTER: Spitschak A 

PROVIDER: S-EPMC11560763 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature