USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer

Cancer Immunol Immunother. 2024 Jun 4;73(8):143. doi: 10.1007/s00262-024-03730-5.

Abstract

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

Keywords: CTL; TIL; Tumor microenvironment; USP47.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Humans
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Lymphocytes, Tumor-Infiltrating* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / immunology
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Tumor Microenvironment

Substances

  • Usp47 protein, mouse