Exploring the Impact of TP53 Mutation and Wild-Type Status on the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer

TP (tumor protein) 53 mutation status plays a critical role in cancer progression and may influence survival outcomes in non-small cell lung cancer (NSCLC) patients receiving immunotherapy. This study investigates the impact of TP53 mutation status and immunotherapy treatment on survival in NSCLC patients. This retrospective study analyzed NSCLC patients treated with pembrolizumab or ipilimumab plus nivolumab, stratified by TP53 mutation status and PD-L1 (programmed death-ligand 1) expression (<1%, 1-49%, >50%). Survival outcomes (overall survival (OS) and progression free survival (PFS) were assessed using Kaplan-Meier curves and log-rank tests, with subgroup analysis by histological subtype. In squamous cell cancer (SCC) patients, no significant differences in OS or PFS were found based on TP53 mutation status or treatment type. A trend toward improved survival was observed with pembrolizumab (<i>p</i> = 0.088). In adenocarcinoma patients, significant differences in OS and PFS were observed based on TP53 mutation status. Pembrolizumab showed superior survival outcomes compared to ipilimumab plus nivolumab in TP53 wild-type patients (<i>p</i> < 0.001). PD-L1 ≥ 1% also predicted better outcomes, especially in adenocarcinoma patients. TP53 mutation status and immunotherapy type significantly influence survival outcomes in NSCLC, particularly in adenocarcinoma patients. Pembrolizumab demonstrated superior efficacy in TP53 wild-type patients, with PD-L1 expression further refining survival predictions. These findings underscore the importance of personalized treatment strategies based on TP53 status and PD-L1 expression in NSCLC. Further studies are needed to validate these results and optimize treatment approaches.

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Journal
International Journal of Molecular Sciences
Published
2025-07-19
DOI
https://doi.org/10.3390/ijms26146939
Citations
1
Primary Topic
Cancer Immunotherapy and Biomarkers
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article
Field-Weighted Citation Impact
1.05
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article

Exploring the Impact of TP53 Mutation and Wild-Type Status on the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer

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1 citations
International Journal of Molecular Sciences
Cancer Immunotherapy and Biomarkers
1.05
article

Exploring the Impact of TP53 Mutation and Wild-Type Status on the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer

Ronen Brenner, Alexander Yakobson, Ashraf Abu Jama, Ahron Yehonatan Cohen, Nooraishah Yasin, Itamar Gothelf, Natalie Maimon Rabinovich, Abed Agbarya, Walid Shalata, Fahmi Abu Ghalion
article en
1 citations

Abstract

TP (tumor protein) 53 mutation status plays a critical role in cancer progression and may influence survival outcomes in non-small cell lung cancer (NSCLC) patients receiving immunotherapy. This study investigates the impact of TP53 mutation status and immunotherapy treatment on survival in NSCLC patients. This retrospective study analyzed NSCLC patients treated with pembrolizumab or ipilimumab plus nivolumab, stratified by TP53 mutation status and PD-L1 (programmed death-ligand 1) expression (<1%, 1-49%, >50%). Survival outcomes (overall survival (OS) and progression free survival (PFS) were assessed using Kaplan-Meier curves and log-rank tests, with subgroup analysis by histological subtype. In squamous cell cancer (SCC) patients, no significant differences in OS or PFS were found based on TP53 mutation status or treatment type. A trend toward improved survival was observed with pembrolizumab (<i>p</i> = 0.088). In adenocarcinoma patients, significant differences in OS and PFS were observed based on TP53 mutation status. Pembrolizumab showed superior survival outcomes compared to ipilimumab plus nivolumab in TP53 wild-type patients (<i>p</i> < 0.001). PD-L1 ≥ 1% also predicted better outcomes, especially in adenocarcinoma patients. TP53 mutation status and immunotherapy type significantly influence survival outcomes in NSCLC, particularly in adenocarcinoma patients. Pembrolizumab demonstrated superior efficacy in TP53 wild-type patients, with PD-L1 expression further refining survival predictions. These findings underscore the importance of personalized treatment strategies based on TP53 status and PD-L1 expression in NSCLC. Further studies are needed to validate these results and optimize treatment approaches.

International Journal of Molecular SciencesVol. 26(14)
Ben-Gurion University of the Negev (IL), Tel Aviv University (IL), Soroka Medical Center (IL), Wolfson Medical Center (IL), Meir Medical Center (IL), Bnai Zion Medical Center (IL)
Openalex Percentile: Top 20%
Cancer Immunotherapy and Biomarkers
1.05
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