TP53 Mutation Status and Biopsy Lesion Type Determine the Immunotherapeutic Stratification in Non-Small-Cell Lung Cancer

Front Immunol. 2021 Sep 17:12:732125. doi: 10.3389/fimmu.2021.732125. eCollection 2021.

Abstract

Immunotherapy, a chemotherapy-free process, has emerged as a promising therapeutic strategy to prolong the overall survival (OS) of patients with non-small-cell lung cancer (NSCLC). However, effective stratification factors for immunotherapy remain unclear. The purpose of this study was to discuss the potential stratification factors of NSCLC immunotherapy using immune checkpoint inhibitors (ICIs) by integrating genomic profiling and tumor lesion-type information. In this study, 344 patients with NSCLC, whose clinical and tissue (including metastatic and primary lesions) mutation information was available, were included. The potential gene mutation status for predicting the outcomes of immunotherapy was screened by comparing the difference in mutation frequency between responders and non-responders. Our results indicated that the potential predictors of immunotherapy were significantly different, especially between patients with TP53(+) (including metastatic and primary lesions) and TP53(-) (including metastatic and primary lesions). According to this classification, patients with NSCLC who suggested immunotherapy had a higher OS than those who did not (25 months vs. 7 months, P < 0.0001, hazard ratio = 0.39). Collectively, this study provides a new perspective for screening immunotherapy predictors in NSCLC, suggesting that the TP53 mutation status and source of biopsy tissue should be considered during the development of immunotherapy biomarkers.

Keywords: TP53 mutation; biomarker; immunotherapy; non-small-cell lung cancer; source of tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Clinical Decision-Making
  • DNA Mutational Analysis
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Mutation*
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • TP53 protein, human
  • Tumor Suppressor Protein p53