Involvement of CCCTC-binding factor (CTCF) in immunomodulation and epigenetic regulation of T helper cell differentiation during Non-Small Cell Lung Cancer (NSCLC)

Recent advances in NSCLC therapy remain limited by treatment resistance, much of which is influenced by epigenetic regulation of immune responses. In this study, we investigate the role of CTCF, a chromatin architectural protein that modulates enhancer-promoter interactions, in shaping T-helper (T_H) cell differentiation and tumor immunity. Changes in CTCF expression coincided with altered chromatin-level enrichment patterns involving DNA repair-associated factors (ERCC1, XPF, CSA) and tumor-related proteins at the IFNG locus, as well as shifts in histone modification marks (H3K4me3 and H3K27me3) at T_H1-associated genes, including TBX21 and IFNG. These chromatin-associated features were accompanied by increased nitric oxide production and enhanced cytotoxicity in functional assays. Collectively, these findings suggest that variation in CTCF levels is linked to coordinated epigenetic and immune-associated changes in NSCLC, supporting its potential relevance as an immuno-epigenetic factor in shaping anti-tumor immune responses.

CRISPR Cas9; CTCF; Epigenetics; NSCLC; T(H)1.