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

Author(s)

Ramos, Rodrigo Nalio ^[1] ; Oliveira, Carine Ervolino ^[1] ; Gasparoto, Thais Helena ^[1] ; de Souza Malaspina, Tatiana Salles ^[1] ; Belai, Eduardo Bertoli ^[1] ; Cavassani, Karen Angelica ^[2] ; Garlet, Gustavo Pompermaier ^[1] ; da Silva, Joao Santana ^[3] ; Campanelli, Ana Paula ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Biol Sci, Bauru Sch Dent, BR-17012901 Bauru, SP - Brazil

^[2] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI - USA

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Carcinogenesis; v. 33, n. 4, p. 902-909, APR 2012.
• Web of Science Citations: 10

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)-1 beta, IL-10, IL-12, IL-13, interferon-gamma, transforming growth factor-beta and tumor necrosis factor-alpha, 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. (AU)

• FAPESP's process: 08/10999-7 - Modulation of immune response during squamous-cell carcinoma development and progression
• Grantee: Ana Paula Campanelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/14127-7 - The role of inflammasomes in chemically induced tumor
• Grantee: Thaís Helena Gasparoto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/03471-9 - Modulation of immune response during squamous-cell carcinoma development and progression
• Grantee: Eduardo Bertoli Belai
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/03859-0 - CD25 T cell depletion impairs murine squamous cell carcinoma development via modulation of antitumor immune responses
• Grantee: Ana Paula Campanelli
• Support Opportunities: Regular Research Grants - Publications - Scientific article