Myeloid-derived suppressor cells contribute to oral cancer progression in 4NQO-treated mice

Oral Dis. 2012 Jan;18(1):67-73. doi: 10.1111/j.1601-0825.2011.01846.x. Epub 2011 Aug 24.

Abstract

Objective: Abnormal myelopoiesis especially the expansion of myeloid-derived suppressor cells (MDSCs) is increasingly recognized as an important reason for the escape of tumor from immune surveillance. This study aims to investigate the role of this specific population of cells in oral cancer progression.

Materials and methods: 4-Nitroquinoline 1-oxide (4NQO) was used to induce oral cancer in C57BL/6 mice. The tongue mucosa was examined by hematoxylin and eosin staining. The distribution of MDSCs in the spleen and peripheral blood and T cell subsets in the spleen was analyzed by flow cytometry. The expression of MDSCs in the tongue tissues was investigated by immunohistochemical staining, and the expression of arginase-1 (ARG-1) and NOS-2 in the tongue tissues was detected by real-time PCR.

Results: We found that during tumor progression, significantly increased frequency of MDSCs was observed in the spleens and peripheral blood of 4NQO-treated mice, and the frequency of MDSCs in the spleens was positively correlated with systemic CD3(+) CD8(+) T cells. Moreover, 4NQO-treated mice showed significantly higher MDSCs infiltration and ARG-1 mRNA level in the tumor site.

Conclusions: Myeloid-derived suppressor cells contribute to oral tumor progression and represent a potential target for immunotherapy of oral cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Nitroquinoline-1-oxide
  • Animals
  • Arginase / analysis
  • CD11b Antigen / immunology
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Flow Cytometry
  • Immune Tolerance / immunology
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / immunology*
  • Nitric Oxide Synthase Type II / analysis
  • Receptors, Chemokine / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Tongue Neoplasms / chemically induced
  • Tongue Neoplasms / immunology*
  • Tongue Neoplasms / pathology
  • Tumor Escape / immunology*

Substances

  • CD11b Antigen
  • Gr-1 protein, mouse
  • Receptors, Chemokine
  • 4-Nitroquinoline-1-oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Arg1 protein, mouse
  • Arginase