STK11, also known as LKB1, encodes the protein liver kinase B1, a serine/threonine kinase involved in multiple physiological processes. It plays a role in regulating cellular metabolism, cell polarity, and the DNA damage response. As a tumour suppressor, it classically acts through the AMP-activated protein kinase-mediated inhibition of the mammalian target of rapamycin signalling pathway [4].

In non-small cell lung cancer (NSCLC), STK11 mutations are associated with poor patient responses to immune checkpoint blockade (ICB). Introduction of a Stk11/Lkb1 mutation into murine lung adenocarcinomas driven by mutant Kras and Trp53 loss led to an ICB-refractory syngeneic KPL tumour due to lack of TCF1-expressing CD8 T cells [3]. Also, STK11-deficient phenotype rather than mutation may better stratify ICB outcomes in NSCLC. STK11-deficient tumours had lost or reversed survival benefit of ICB compared to chemotherapy, and were associated with perturbed STING/interferon-I signalling and CD8+ T-cell dysfunction [1]. In lung adenocarcinoma, concurrent STK11 and KEAP1 loss-of-function mutations result in elevated expression of ferroptosis-protective genes and resistance to pharmacologically induced ferroptosis, with SCD1 being selectively essential in this co-mutant subtype [2].

In summary, STK11 is a crucial gene involved in multiple biological functions and tumour suppression. Its role in NSCLC, especially in relation to immunotherapy response and ferroptosis regulation, has been revealed through in vivo models. These findings provide important insights into disease mechanisms and potential therapeutic targets in NSCLC [1,2,3].