ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Divergent Clinical and Immunologic Outcomes Based on STK11 Co-mutation Status in Resectable KRAS-Mutant Lung Cancers Following Neoadjuvant Immune Checkpoint Blockade.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- Investigation of the Prevalence of Associated Genetic Mutations (Co-Mutations) in Patients with Actionable Driver Mutations in Lung Cancer: A Retrospective Study.Diagnostics (Basel, Switzerland) · 2026Article
- The landscape of responses to neoadjuvant immunotherapy in resectable Kirsten rat sarcoma viral oncogene homolog-mutant lung adenocarcinoma: Clinical heterogeneity and correlative immunologic analysis.Clinical and translational medicine · 2026Article
- Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review).Oncology reports · 2026Review
- Neoadjuvant and perioperative immunotherapy in resectable non-small cell lung cancer: Evidence to date and remaining questions.JTCVS open · 2026Article
- Immune checkpoint inhibitors in resectable non-small cell lung cancer: recent successes and ongoing challenges.Frontiers in oncology · 2026Review
- Neoadjuvant immunotherapy for lung cancer: current limitations and future prospects.Frontiers in immunology · 2026Review
- PGE1 Suppresses the Expression of M2 Markers on Macrophages Through Prostaglandin Receptors.Cells · 2025Article
- Article
- Decoding the immune landscape:Translational lung cancer research · 2025Article
- Article
- Perioperative Therapy in Oncogene-Driven Non-Small Cell Lung Cancer: Current Strategies and Unanswered Questions.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2025Review
- The role of immunotherapy in resectable non-small-cell lung cancer.Therapeutic advances in medical oncology · 2025Review
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Abstract
purposeCo-mutations of the Kirsten rat sarcoma virus (KRAS) and serine/threonine kinase 11 (STK11) genes in advanced non-small cell lung cancer (NSCLC) are associated with immune checkpoint blockade (ICB) resistance. Although neoadjuvant chemoimmunotherapy is now a standard-of-care treatment for resectable NSCLC, the clinical and immunologic impacts of KRAS and STK11 co-mutations in this setting are unknown. EXPERIMENTAL
designWe evaluated and compared recurrence-free survival of resectable KRAS-mutated NSCLC tumors, with or without co-occurring STK11 mutations, treated with neoadjuvant ICB. Single-cell transcriptomics was performed on tumor-infiltrating T cells from seven KRASmut/STK11wt tumors and six KRAS and STK11 co-mutated (KRASmut/STK11mut) tumors.
resultsRelative to KRASmut/STK11wt tumors, KRASmut/STK11mut exhibited significantly higher recurrence risk. Single-cell transcriptomics showed enhanced oxidative phosphorylation with evidence of decreased prostaglandin E2 signaling and increased IL-2 signaling in CD8+ tumor-infiltrating lymphocytes (TIL) from KRASmut/STK11mut tumors, a finding that was mirrored in KRASwt tumors that relapsed. TILs from KRASmut/STK11mut tumors expressed high levels of molecules associated with tumor residence, including CD39 and ZNF683 (HOBIT).
conclusionsThese divergent T-cell transcriptional fates suggest that T-cell maintenance and residence may be detrimental to antitumor immunity in the context of neoadjuvant ICB for resectable NSCLC, regardless of KRAS mutation status. Our work provides a basis for future investigations into the mechanisms underpinning prostaglandin E2 signaling and IL-2 signaling as they relate to T-cell immunity to cancer and to divergent clinical outcomes in KRASmut/STK11mut NSCLC treated with neoadjuvant ICB.
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