University of Pittsburgh, Pittsburgh, Pa;
University of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany;
LMU Medical Center, Munich, Germany
Objective: Overexpression of COX-2 is associated with PGE2 production in head and neck squamous cell carcinoma (HNSCC) (Tu). This milieu promotes induction and accumulation of interleukin (IL)-10/antigen-dependent regulatory T cells (Tr1).
Methods: A coculture system was established that consisted of COX-2+ HNSCC (Tu) cell line, CD4+CD25+ or CD4+CD25− T cells obtained from normal donors and autologous immature dendritic cells (iDC). IL-2, IL-10, and IL-15 were added and cultures incubated for 7 days. The system was modified by addition of synthetic prostaglandin E2 (PGE2) (26mM) in Tu absence or of rapamycin (1nM), which expands Tr1 cells. Flow cytometry for Tr1 phenotype (CD3, CD4, CD25, CD25, FOXP3, GITR, CTLA4, IL-10, IL-2Rβ/γ, and Fas) and CFSE proliferation with CD4+CD25− autologous T cells as responders to measure Tr1 function were performed. Inhibition of responses with or without Tr1 to OKT3 and anti-CD28 Ab was determined.
Bergmann C, Strauss L, Lang S, Zeidler R, Whiteside TL. P102 Induction of IL-10+ Tr1-Like Regulatory T Cells in the Microenvironment of COX-2+ Head and Neck Squamous Cell Carcinoma. Arch Otolaryngol Head Neck Surg. 2006;132(8):885. doi:10.1001/archotol.132.8.885-c