Research Paper Advance Articles

TP53 somatic mutations are associated with poor survival in non-small cell lung cancer patients who undergo immunotherapy

Liqin Zhao1,2, *, , Xiaofei Qu2,3, *, , Zhenhua Wu1,2, , Yuehua Li4, , Xiaowei Zhang1,2, , WeiJian Guo1,2, ,

  • 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
  • 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
  • 3 Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China
  • 4 Department of Medical Oncology, The First Affiliated Hospital of University of South China, Hunan, China
* Equal contribution

Received: March 3, 2020       Accepted: June 4, 2020       Published: July 22, 2020      

https://doi.org/10.18632/aging.103502
How to Cite

Copyright © 2020 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

In this study, we investigated the association between TP53 somatic mutations and immunotherapeutic outcomes in non-small cell lung cancer (NSCLC) patients. Kaplan-Meier survival curve analysis of the MSK-IMPACT cohort of 350 NSCLC patients shows that overall survival (OS) is significantly lower for patients with truncating TP53 mutations than those with wild-type TP53 (OS: 9 months vs. 14 months; P=0.019). Multivariate analysis shows that truncating TP53 mutations are an independent predictor of immunotherapeutic outcomes. Moreover, among NSCLC patients with lower tumor mutation burden (TMB), those with TP53 truncating mutations showed significantly lower OS than those with wild-type TP53 [hazard ratio (HR) = 1.40, confidence interval (CI) = 1.13-1.73; P = 0.002]. TP53 mutations correlate with higher infiltration of CD8+ T cells, neutrophils and dendritic cells in lung adenocarcinoma tissues. A prognostic model with TP53 mutational status shows better survival prediction than the model without TP53 mutational status 1-year [area under curve (AUC): 64.9% vs. 60.2%; P = 0.052] and 2-years (AUC: 70.9% vs. 66.1%; P = 0.098) post-immunotherapy. These findings demonstrate that truncating TP53 mutations correlate with poor immunotherapy outcomes in NSCLC patients with low TMB. TP53 mutation status also improves the prognostic prediction in NSCLC patients that underwent immunotherapy.

Abbreviations

ICI: immune checkpoint inhibitors; NSCLC: non-small cell lung cancer; OS: overall survival; PFS: progression free survival; HR: hazard ratio; CI: confidence interval; TMB: tumor mutation burden; EGFR-TKI: epidermal growth factor receptor tyrosine kinase inhibitors; ALK: anaplastic lymphoma kinase; ROS1: c-ros oncogene 1 receptor kinase; PD-1: programmed cell death protein 1; PD-L1: programmed cell death-ligand 1; CTLA4: cytotoxic T-lymphocyte-associated protein 4; MSK-IMPACT: Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets; MSK: Memorial Sloan Kettering; KM: Kaplan-Meier; ROC: receiver operating characteristic; TIMER: Tumor Immune Estimation Resource; AUC: area under curve.