INCREASED PREVALENCE OF INTERLEUKIN-17-PRODUCING CD4+ TUMOR INFILTRATING LYMPHOCYTES IN HUMAN ORAL SQUAMOUS CELL CARCINOMA

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-1 beta, IL-6, and transforming growth factor (TGF)-beta. 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. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 1301-1308, 2011