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

• Published in: Carcinogenesis (New York) 2012-04, Vol.33 (4), p.902-909
• Main Authors: NALIO RAMOS, Rodrigo, ERVOLINO OLIVEIRA, Carine, HELENA GASPAROTO, Thais, DE SOUZA MALASPINA, Tatiana Salles, BERTOLI BELAI, Eduardo, ANGELICA CAVASSANI, Karen, POMPERMAIER GARLET, Gustavo, DA SILVA, Joao Santana, PAULA CAMPANELLI, Ana
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cytokines - metabolism; Dermatology; Female; Interleukin-2 Receptor alpha Subunit - immunology; Lymphocyte Depletion; Medical sciences; Mice; Mice, Inbred BALB C; T-Lymphocytes - immunology; Tumors; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgs103

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.