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Original Article
Association of TP53 Mutation Status and Sex with Clinical Outcome in NSCLC Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study
Songji Choi1orcid , Se Hyun Kim1orcid , Sejoon Lee2, Jeongmin Seo1, Minsu Kang1, Eun Hee Jung1, Sang-A Kim1, Koung Jin Suh1, Ji Yun Lee1, Ji-Won Kim1, Jin Won Kim1, Jeong-Ok Lee1, Yu Jung Kim1, Keun-Wook Lee1, Jee Hyun Kim1,2, Soo-Mee Bang1, Jong Seok Lee1

DOI: https://doi.org/10.4143/crt.2024.046 [Accepted]
Published online: August 7, 2024
1Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
2Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam, Korea
Corresponding author:  Se Hyun Kim
Tel: 82-31-787-7071 Fax: 82-31-787-4098 Email: sehyunkim@snubh.org
Received: 15 January 2024   • Accepted: 6 August 2024
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Purpose
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of TCGA and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results
In SNUBH cohort, no statistically significant difference was observed in disease control rate per the TP53 mutation status (p=0.503); however, female patients with TP53 mutated (MT) had a significantly prolonged median progression-free survival (PFS) compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). PD-L1 high (≥50%) expression was significantly enriched in female patients with TP53 MT (p=0.001). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p<0.001). In TCGA analysis, expression of immune-related genes, and TMB score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.


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