The LDH-H3K18La-Nur77 Axis Potentiates Immune Escape in Small Cell Lung Cancer.

ABSTRACT: Small cell lung cancer (SCLC) remains a therapeutic challenge due to its aggressive nature and limited response to immunotherapy. This study identifies lactate-induced histone lactylation as a novel epigenetic mechanism in SCLC, contributing to immune escape and poor therapeutic outcomes. By identifying the LDH-H3K18La-Nur77 axis, new insights into the metabolic regulation of immune responses in SCLC are offered. Multi-omics analysis, including metabolomics and TCR sequencing, is used to compare serum samples and immune cell profiles from SCLC patients. Data from Shanzhong cohort (n = 222), along with a validation cohort from the IMpower133 study (n = 264), demonstrates that LDH levels are associated with poorer outcomes following immunotherapy. ChIP-qPCR and luciferase reporter assays rev

SUBMITTER: Shang X 

PROVIDER: S-EPMC12442664 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature