STK11 deletion + TTF1 positive

This is a retrospective and descriptive study across eight transcriptomic datasets of 2118 non-squamous NSCLC with 314 STK11 mutations, including 628 patients randomized to docetaxel or atezolizumab in the OAK and POPLAR clinical trials. STK11-DPC is highly predictive of immune exclusion and NSCLC patient outcomes. It identifies STK11-deficient subsets with increased immune infiltration and improved ICB response, and two putatively immune-resistant subgroups with markedly different TME phenotypes: Neuroendocrine tumors have an anti-inflammatory phenotype, while TTF1-Low tumors exhibit chronic inflammation. Performance of STK11-DPC as a predictive biomarker warrants further validation in additional patient cohorts, while the apparent TME differences suggest distinct and non-overlapping mechanisms of ICB resistance and may guide development of precision treatment strategies.