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

Resumo

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 ofregulatory T cells (Tregs) has been associated with the suppression of tumor-reactive T cells. However, the underlying mechanismfor 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 ananti-CD25 monoclonal antibody (PC61) resulted in a decrease in the number and incidence of papilloma. Furthermore, CD25 depletionincreased the proportion of CD81 and CD41 T cells that were isolated from tumor lesions. The levels of interleukin (IL)-1b, IL-10, IL-12, IL-13, interferon-g, transforming growth factorband tumor necrosis factor-a, but not IL-17, were increased in the tumor microenvironment after Treg depletion. Therefore, our results indicated involvement of CD251 T cells in SCC developmentand in the suppression of the inflammatory immune response. (AU)