Cancer-derived matrix metalloproteinase-9 contributes to tumor tolerance

J Cancer Res Clin Oncol. 2011 Oct;137(10):1525-33. doi: 10.1007/s00432-011-1010-4. Epub 2011 Aug 11.

Abstract

Background and aims: Tumor-specific T regulatory cells (Treg) play a critical role in tumor cell survival. The development of tumor-specific Treg is not fully understood. This study aims to elucidate the role of matrix metalloproteinase (MMP)9 in tumor tolerance development.

Methods: We recruited 38 patients with laryngeal cancer (LC) in this study. MMP9 levels in the LC were measured by western blotting. Immune cells were isolated from LC tissue for indicated experiments. The cells' activities were characterized by flow cytometry.

Results: High levels of MMP9 were detected in LC that plays a critical role in the development of tolerogenic dendritic cells and LC-specific Tregs. The isolated LC Tregs have the ability to suppress tumor-specific CD8 T cells in a tumor antigen-specific manner.

Conclusions: This study reveals a novel mechanism in tumor tolerance in which MMP9 plays a critical role in tumor survival. The data imply that MMP9 may be a potential target in the treatment of malignant tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology
  • GPI-Linked Proteins / physiology
  • Humans
  • Immune Tolerance*
  • Laryngeal Neoplasms / enzymology
  • Laryngeal Neoplasms / immunology*
  • Matrix Metalloproteinase 9 / physiology*
  • T-Lymphocytes, Regulatory / physiology
  • Transforming Growth Factor beta / physiology

Substances

  • GPI-Linked Proteins
  • RECK protein, human
  • Transforming Growth Factor beta
  • Matrix Metalloproteinase 9