CD25+ T cell depletion impairs murine squamous cell carcinoma development via modulation of antitumor immune responses

Carcinogenesis. 2012 Apr;33(4):902-9. doi: 10.1093/carcin/bgs103. Epub 2012 Feb 16.

Abstract

Squamous cell carcinoma (SCC) constitutes a microenvironment that could modulate the antitumor immune response. Also, tumor-infiltrating lymphocytes are believed to play complex regulatory roles in antitumor immunity against SCC. The presence of regulatory T cells (Tregs) has been associated with the suppression of tumor-reactive T cells. However, the underlying mechanism for this T cell dysfunction is not clear. We used a multistage model of SCC to examine the role of Treg cells during tumor development. 7,12-dimethylbenz[a]-anthracene/phorbol 12-myristate 13-acetate treatment and systemic depletion of Treg cells using an anti-CD25 monoclonal antibody (PC61) resulted in a decrease in the number and incidence of papilloma. Furthermore, CD25 depletion increased the proportion of CD8(+) and CD4(+) T cells that were isolated from tumor lesions. The levels of interleukin (IL)-1β, IL-10, IL-12, IL-13, interferon-γ, transforming growth factor-β and tumor necrosis factor-α, but not IL-17, were increased in the tumor microenvironment after Treg depletion. Therefore, our results indicated involvement of CD25(+) T cells in SCC development and in the suppression of the inflammatory immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cytokines / metabolism
  • Female
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Lymphocyte Depletion*
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes / immunology*

Substances

  • Cytokines
  • Interleukin-2 Receptor alpha Subunit