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Narrative review examines driver mutations and immunotherapy response in non-small cell lung cancer

Narrative review examines driver mutations and immunotherapy response in non-small cell lung cancer
Photo by Giovanni Crisalfi / Unsplash
Key Takeaway
Note that immunotherapy efficacy varies markedly across NSCLC molecular subtypes defined by targetable driver gene alterations.

This narrative review addresses the impact of targetable driver gene alterations, including EGFR, ALK, KRAS, MET, RET, and BRAF mutations, on the tumor immune microenvironment in patients with non-small cell lung cancer. The scope encompasses how these oncogenic drivers actively shape the microenvironment by regulating antigen presentation, immune cell infiltration, cytokine signaling, metabolic programs, and immune checkpoint expression. The review does not report specific sample sizes, absolute numbers, or statistical measures such as p-values or confidence intervals.

The authors note that the efficacy of immunotherapy varies markedly across molecular subtypes defined by these targetable driver gene alterations. While the review provides a rationale for precision immunotherapy strategies and the design of biomarker-driven clinical trials, it does not present pooled effect sizes or adverse event rates. Consequently, the evidence remains qualitative rather than quantitative.

Limitations acknowledged by the authors include the absence of reported follow-up durations and specific safety data. The review does not establish causal relationships or provide definitive trial-level data. Clinicians should interpret these findings as a conceptual framework rather than evidence for specific dosing or outcome predictions in individual patients.

Study Details

Study typeSystematic review
EvidenceLevel 1
PublishedApr 2026
View Original Abstract ↓
Non-small cell lung cancer (NSCLC) is characterized by substantial molecular heterogeneity that critically influences the efficacy of immunotherapy. Although immune checkpoint inhibitors (ICIs) have improved outcomes in selected patients, responses vary markedly across molecular subtypes defined by targetable driver gene alterations. Increasing evidence indicates that oncogenic drivers, including EGFR, ALK, KRAS, MET, RET, and BRAF, actively shape the tumor immune microenvironment (TIME) by regulating antigen presentation, immune cell infiltration, cytokine signaling, metabolic programs, and immune checkpoint expression. These interactions generate distinct driver gene–associated immune phenotypes that underlie differential sensitivity and resistance to ICIs. Recent advances in single-cell and spatial profiling have further revealed the complexity and spatial organization of these immune landscapes. In this review, we summarize current mechanistic and clinical evidence supporting the targetable driver gene–TIME axis in NSCLC and discuss its implications for immunotherapy response, resistance, and patient stratification. This integrative framework provides a rationale for precision immunotherapy strategies and the design of biomarker-driven clinical trials.
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