STK11/LKB1 and Immune Phenotypes Co-Determine Immunotherapy Outcomes

We appreciate Amori et al. for their valuable comments on our article. 1 Li A, Wang Y, Yu Z, et al. STK11/LKB1-deficient phenotype rather than mutation diminishes immunotherapy efficacy and represents STING/type I interferon/CD8+ T-cell dysfunction in NSCLC [e-pub ahead of print]. J Thorac Oncol. https://doi.org/10.1016/j.jtho.2023.07.020. Accessed August 24, 2023. Google Scholar This work used three high-quality randomized controlled trials (RCTs) to present the negative impact of the STK11-deficient (STK11-def) phenotype beyond mutation on immune checkpoint blockade (ICB) efficacy in NSCLC. 1 Li A, Wang Y, Yu Z, et al. STK11/LKB1-deficient phenotype rather than mutation diminishes immunotherapy efficacy and represents STING/type I interferon/CD8+ T-cell dysfunction in NSCLC [e-pub ahead of print]. J Thorac Oncol. https://doi.org/10.1016/j.jtho.2023.07.020. Accessed August 24, 2023. Google Scholar A recent proteogenomic study suggested that down-regulation of STK11 is also crucial for lung tumors lacking STK11 mutations, 2 Li Y. Porta-Pardo E. Tokheim C. et al. Pan-cancer proteogenomics connects oncogenic drivers to functional states. Cell. 2023; 186: 3921-3944.e25 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar further emphasizing the necessity to evaluate the STK11 phenotype. Here, we address the question of whether STK11 phenotype, CD274 mRNA expression, and Estimation of STromal and Immune cells in MAlignant Tumours using Expression data immune score (EIS) can be integrated into a predictive biomarker panel. Leveraging Transcriptomics Data to Refine Immunotherapy Response Prediction in NSCLC: STK11 Deficiency and BeyondJournal of Thoracic OncologyVol. 18Issue 11PreviewWe read the article by Li et al.,1 recently published in the Journal of Thoracic Oncology, with great interest. The authors reported that the STK11-deficient phenotype, rather than mutation, is associated with a reduced response to immune checkpoint blockade (ICB) therapy in NSCLC by evaluating the ORIENT-11, OAK, and POPLAR trials, and The Cancer Genome Atlas–NSCLC cohort. Furthermore, they revealed underlying mechanisms such as depleted STING and interferon-I activity and CD8-positive T-cell dysfunction in STK11-deficient tumors. Full-Text PDF