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August 6, 2025Journal for ImmunoTherapy of CancerOpen Access

Genetic drivers of tumor microenvironment and immunotherapy resistance in non-small cell lung cancer: the role of KEAP1, SMARCA4, and PTEN mutations

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Authors

RPRodrigo ParedesRBRoberto BoreaFDFrancesco Drago

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Overview

Review examines genetic mutations in KEAP1, SMARCA4, and PTEN affecting immunotherapy resistance in NSCLC, highlighting implications for treatment.

Key Points

  • Main finding shows that KEAP1, SMARCA4, and PTEN mutations drive immunotherapy resistance in nonsmall cell lung cancer.
  • Key evidence suggests these mutations create an immune-excluded tumor microenvironment that reduces T-cell infiltration.
  • Approach involved exploring how chromatin remodeling and the PI3K/AKT pathway affect tumor immunogenicity and response to treatment.
  • Significance lies in identifying these genetic alterations to tailor immunotherapy strategies and improve patient outcomes.

Cite This Study

Paredes et al. (2025) studied this question.

synapsesocial.com/papers/689a0f99e6551bb0af8d1563https://doi.org/10.1136/jitc-2025-012288
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Overcoming immunotherapy resistance in non-small cell lung cancer: a narrative review of related factors2025
  2. 2Dissecting the immune evasion and therapeutic resistance mechanisms in EGFR/TP53 co-mutated non-small cell lung cancer: implications for targeted and immunotherapy strategies2025 · 5 citations
  3. 3Immunotherapy resistance in non-small cell lung cancer: from mechanisms to therapeutic opportunities2025
  4. 4Tumor Microenvironmental Dynamics in Shaping Resistance to Therapeutic Interventions in Melanoma: A Narrative Review2025 · 13 citations
  5. 5Immune Evasion and Resistance in Cancer Progression: Overcoming Checkpoint Inhibition Challenges with Personalized Immunotherapy Guided by PD-L1 Expression2025 · 1 citations