KDM1A is a crucial epigenetic modulator in tumor immune escape. Nevertheless, its precise regulatory function within the immune microenvironment of lung cancer needs investigation. Using TCGA data, we analyzed KDM1A and SBNO2 expression, clinical correlation, and immune infiltration. Functional assays included co-culture of lung cancer cells with CD8+ T cells, flow cytometry, Transwell migration, ChIP, and luciferase reporter assays. qPCR measured gene expression. KDM1A and SBNO2 were notably upregulated in lung cancer tissues, which correlated with poor patient prognosis and reduced CD8+ T cell infiltration. Functional experiments demonstrated that knockdown of KDM1A enhanced T cell proliferation, chemotaxis, and cytokine production. Mechanistically, KDM1A acted as a transcription regulator binding to the SBNO2 promoter and positively regulated its mRNA expression in lung cancer cells. Importantly, rescue experiments confirmed that silencing SBNO2 expression abolished the pro-tumor immune escape effects induced by KDM1A overexpression. This study unveils a novel mechanism whereby KDM1A drives immune escape in lung cancer by transcriptionally activating SBNO2, which subsequently suppresses the anti-tumor role of CD8+ T cells. These findings lend strong support to targeting the KDM1A-SBNO2 axis as a promising immunotherapeutic approach for lung cancer.
Pan et al. (Sun,) studied this question.