Study provides genomic insights into treatment resistance in SMARCA4-mutant lung cancer
MD Anderson Research Highlight March 18, 2025
SMARCA4 ¨C a gene that helps in chromatin remodeling ¨C frequently is mutated in lung cancer, leading to immunotherapy resistance and a poor prognosis. To understand the underlying mechanisms, researchers led by , examined its role in lab models of SMARCA4-mutant lung cancer. SMARCA4 loss led to a decreased response to anti-PD1 immunotherapy and was associated with lower infiltration of CD4+ T cells and dendritic cells in the tumor microenvironment. The study showed that cancer cells with these mutations reprogram the tumor microenvironment by reducing chromatin accessibility at key enhancers of immune-related genes, such as the STING pathway. The researchers also found enrichment of NF-kB on these enhancers, suggesting a functional link between NF-kB and SMARCA4 in regulating immune and inflammatory gene expression. These findings suggest potential therapeutic strategies that boost dendritic cells or the STING pathway to overcome immunotherapy resistance in SMARCA4-mutant tumors. Learn more in .
These findings highlight the relevance of cancer-cell intrinsic genomic alterations as modifiers of immunotherapy response. Furthermore, this study provides compelling evidence for the role of chromatin remodelers in expression of STING, an emerging target for cancer immunotherapy.