ACAT1 regulates tertiary lymphoid structures: A target for enhancing immunotherapy in non–small cell lung cancer

Non–small cell lung cancer (NSCLC), the most common type of lung cancer, remains a leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have emerged as a promising therapy for NSCLC but only benefit a subset of patients. In this issue of the JCI, Jiao et al. revealed that acetyl-CoA acetyltransferase 1 (ACAT1) limited the efficacy of ICIs in NSCLC by impeding tertiary lymphoid structures (TLS) in the tumor microenvironment (TME). Targeting ACAT1 in tumor cells reduced mitochondrial hypersuccinylation and oxidative stress, enhancing TLS abundance and improving the efficacy of ICIs in preclinical murine models of NSCLC.