Effect of NCOR1 Mutations on Immune Microenvironment and Efficacy of Immune Checkpoint Inhibitors in Patient with Bladder Cancer

Front Immunol. 2021 Mar 8:12:630773. doi: 10.3389/fimmu.2021.630773. eCollection 2021.

Abstract

Immune checkpoint blockade (ICB) therapy has significantly progressed the treatment of bladder cancer (BLCA). Multiple studies have suggested that specific genetic mutations may serve as immune biomarkers for ICB therapy. Additionally, the nuclear receptor corepressor 1 (NCOR1) gene is a new player in the field of immune tolerance and the development of immune cells. In the ICI-treated-cohort, NCOR1 mutations may be used as a biomarker to predict the prognosis of BLCA patients receiving ICIs. The overall survival (OS) of the NCOR1-mutant (NCOR1-MT) group was significantly longer than that of NCOR1-wild-type (NCOR1-WT) group (P = 0·031; HR [95%CI]: 0·25 [0·12-0·52]). In the TCGA-BLCA-cohort, compared with NCOR1-WT, NCOR1-MT was associated with known predictors of ICB therapy efficacy, such as higher tumor mutational burden (TMB), neoantigen load and the number of mutations in the DNA damage-repair pathway. In addition, NCOR1-MT tumors had highly infiltrating TILs, activated antitumor immunity, and a high expression of immune-related genes, suggesting that NCOR1 mutations may serve as a potential biomarker to guide ICB therapy in BLCA.

Keywords: bladder cancer; immune checkpoint inhibitor; mutations; nuclear receptor corepressor 1 (NCOR1); tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Mutation*
  • Nuclear Receptor Co-Repressor 1 / genetics*
  • Tumor Microenvironment*
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / mortality

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • NCOR1 protein, human
  • Nuclear Receptor Co-Repressor 1