Open Access

Increased pressure stimulates aberrant dendritic cell maturation

  • David H. Craig1, 4,
  • Keri L. Schaubert4,
  • Hiroe Shiratsuchi1,
  • June Kan-Mitchell4 and
  • Marc D. Basson1, 2, 3, 4Email author
Cellular & Molecular Biology LettersAn International Journal200813:260

DOI: 10.2478/s11658-007-0054-6

Received: 8 October 2007

Accepted: 6 December 2007

Published: 10 April 2008

Abstract

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.

Key words

Pressure Dendritic cell Maturation Cancer Immunosurveillance

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