Transcriptional activation of FGL1 by KDM1A promotes immune evasion in lung cancer.

Abstract

Immunotherapy is often thwarted by the innate ability of cancer to evade immune detection. Lysine-specific demethylase 1A (KDM1A/LSD1) has been implicated in the development of various cancers, yet its specific influence on immune evasion in lung cancer and the mechanisms at play are not well defined in the current scientific discourse. Through bioinformatics, we probed the expression patterns of KDM1A and fibrinogen-like protein 1 (FGL1) in lung cancer continues with cellular validation. Lactate dehydrogenase (LDH) and enzyme-linked immunosorbent assay were used for the assessment of CD8⁺ T-cell responses to tumor cells. To uncover the molecular underpinnings, we use a suite of techniques including bioinformatics, luciferase reporter assays, chromatin immunoprecipitation, and qRT-PCR. Bioinformatics pointed to a positive relationship between KDM1A and FGL1, with both markers highly expressed in lung cancer. KDM1A was found to dampen the cytotoxicity of CD8⁺ T cells toward lung cancer cells through its transcriptional activation of FGL1. Our work reveals the role of KDM1A in lung cancer immune evasion by transcriptionally activating FGL1, which could inform the design of new immunotherapies.NEW & NOTEWORTHY KDM1A and FGL1 exhibit high expression in lung cancer. KDM1A expression is associated with immune evasion in tumors. KDM1A regulates FGL1, thereby influencing the antitumor activity of CD8⁺ T cells in lung cancer.