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STK11 ICI Resistance — SCE Medical Oncology MCQ

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HardLung CancerSTK11 ICI ResistanceSCE Medical Oncology

A 65-year-old man with stage IV NSCLC has STK11/KRAS co-mutation on molecular profiling. His PD-L1 TPS is 60%. How does STK11 mutation affect immunotherapy outcomes?

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Correct answer: D — STK11 (LKB1) mutations are associated with an immunologically 'cold' tumour microenvironment and reduced benefit from PD-1/PD-L1 inhibitors — even with high PD-L1 expression; this represents a negative predictive biomarker for ICI in NSCLC

STK11/LKB1 mutations (~15% NSCLC, often co-occurring with KRAS) create an immunologically cold TME: reduced MHC-I expression, decreased T-cell infiltration, impaired STING pathway. Multiple retrospective analyses show reduced ICI benefit regardless of PD-L1 status. This limits PD-L1 as a standalone predictive biomarker. KEAP1 co-mutation further worsens ICI outcomes.

Reference: ESMO 2024 NSCLC; Skoulidis et al Cancer Discov 2018