Increased prevalence of interleukin-17-producing CD4 + tumor infiltrating lymphocytes in human oral squamous cell carcinoma

Abstract

Background. T helper 17 (Th17) and regulatory T cells share plasticity in the expression of interleukin (IL)-17 and forkhead box P3 (FOXP3), but their mutual presence in human diseases is unclear. Methods. IL-17 and FOXP3 were analyzed by immunohistostaining and flow cytometry. The cytokine milieu was analyzed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results. Oral squamous cell carcinoma expresses high levels of IL-1β, IL-6, and transforming growth factor (TGF)-β. A unique subset of FOXP3 + IL-17-producing CD4 + T cells was consistently identified in tumor-infiltrating lymphocytes from advanced stages of cancer, but not in the circulation, at a frequency of 0.5% to 5.5 % of total CD4 + T and positively correlated with the frequency of IL-17 +FOXP3 - T cells. The IL-17 +FOXP3 + T cells express CCR6 and suppress the proliferation of autologous CD4 + CD25 - responder T-cells in vitro. Conclusions. The prevalence of IL-17-producing FOXP3 + CD4 + tumor infiltrating lymphocytes is increased in oral squamous cell carcinoma. ? 2010 Wiley Periodicals, Inc. Head Neck, 2010 Copyright ? 2010 Wiley Periodicals, Inc.