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Updated: Jan 17, 2026

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
A retrospective analysis of immunotherapy in non-small cell lung cancer patients with targetable genetic mutations
Shiyu Zhang1, Jingwen Liu2, Jia Liu3
1Department of Respiratory and Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, P.R. China.
Abstract:
Targeted therapy has greatly improved the survival time and quality of life of some patients with non-small cell lung cancer. The application of immunotherapy among populations without targetable oncogenes has also achieved great success. However, the decision is still inconclusive as to whether immunotherapy can be used in targeted populations. We screened studies related to immunotherapy for lung cancer from public data platforms and then rearranged the cases. We grouped these cases according to driver genes and analyzed the impact of different targetable genes on immunotherapy (including mono-immunotherapy and combined immunotherapy). In addition, we also identified the predictive efficacy of programmed death-ligand 1 and tumor mutation burden on immunotherapy in populations with different driver genes. We identified 926 cases of lung cancer doing immunotherapy, including 321 cases in the driver gene negative group, 289 cases in the non-sensitive mutations group, and 316 cases in the sensitive mutations group. Except for KRAS and BRAF-sensitive mutations, the other sensitive mutations seemed to impede the effectiveness of immunotherapy. While among the non-sensitive mutations, aside from the EGFR group, the others exhibited immune benefits. The predictive effects of programmed death-ligand 1 and tumor mutation burden on immunotherapy were no longer uniform in mono or combined immunotherapy and needed to be discussed separately. Our data suggest that certain driver gene mutations may influence the response to immunotherapy, though further validation in larger cohorts is needed to confirm these observations. Combined immunotherapy is also different from mono-immunotherapy in many aspects, so we need to consider it separately according to different situations in clinical treatment.
Insights
Driver gene mutations in non-small cell lung cancer impact immunotherapy effectiveness. Certain mutations may hinder response, while others show benefits, necessitating personalized treatment strategies for optimal outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Targeted therapy and immunotherapy have advanced non-small cell lung cancer (NSCLC) treatment.
- The role of immunotherapy in patients with targetable oncogenes remains under investigation.
- Understanding driver gene mutations is crucial for optimizing NSCLC immunotherapy.
Purpose of the Study:
- To analyze the impact of driver gene mutations on immunotherapy efficacy in NSCLC.
- To evaluate programmed death-ligand 1 (PD-L1) and tumor mutation burden (TMB) as predictive biomarkers across different mutation groups.
- To differentiate the effects of mono-immunotherapy versus combined immunotherapy based on genetic profiles.
Main Methods:
- Retrospective analysis of 926 NSCLC immunotherapy cases from public data.
- Grouping cases based on driver gene status: negative, non-sensitive mutations, and sensitive mutations.
- Assessment of immunotherapy response in relation to specific gene mutations (e.g., KRAS, BRAF, EGFR) and biomarkers (PD-L1, TMB).
Main Results:
- Sensitive mutations (excluding KRAS, BRAF) generally reduced immunotherapy effectiveness.
- Non-sensitive mutations, except for EGFR, showed immune benefits.
- PD-L1 and TMB predictive efficacy varied between mono- and combined immunotherapy, requiring separate consideration.
Conclusions:
- Specific driver gene mutations in NSCLC can influence immunotherapy response.
- Treatment decisions for immunotherapy should account for individual patient mutation profiles.
- Further large-scale studies are needed to validate these findings and refine clinical strategies for NSCLC immunotherapy.
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