Increased pressure stimulates aberrant dendritic cell maturation

• Published in: Cellular & molecular biology letters 2008-06, Vol.13 (2), p.260-270
• Main Authors: Craig, David, Schaubert, Keri, Shiratsuchi, Hiroe, Kan-Mitchell, June, Basson, Marc
• Format: Article
• Language: English
• Subjects: Cancer; Cell Differentiation; Cell Line, Tumor; Dendritic cell; Dendritic Cells - cytology; Extracellular Space - metabolism; Histocompatibility Antigens - metabolism; Humans; Immunosurveillance; Interleukin-12 - biosynthesis; Maturation; Phagocytosis; Phenotype; Pressure
• ISSN: 1689-1392; 1425-8153; 1689-1392
• DOI: 10.2478/s11658-007-0054-6

Patients with malignancy typically exhibit abnormal dendritic cell profiles. Interstitial tumor pressure is increased 20-50mmHg over that in normal tissue. We hypothesized that elevated pressure in the tumor microenvironment may influence dendritic cell (DC) phenotype and function. Monocyte-derived immature and mature DC isolated from healthy human donors were exposed to either ambient or 40 mmHg increased pressure at 37°C for 12 hours, then assessed for expression of CD80, CD86, CD83, CD40, MHC-I and MHC-II. IL-12 production and phagocytosis of CFSE-labeled tumor lysate were assessed in parallel. Elevated pressure significantly increased expression of all co-stimulatory and MHC molecules on mature DC. Immature DC significantly increased expression of CD80, CD86, CD83 and MHC-II, but not MHC-I and CD40, versus ambient pressure controls. Pressure-treated immature DC phenotypically resembled mature DC controls, but produced low IL-12. Phenotypic maturation correlated with decreased phagocytic capacity. These results suggest increased extracellular pressure may cause aberrant DC maturation and impair tumor immunosurveillance.