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. 2008 Apr 10;13(2):260. doi: 10.2478/s11658-007-0054-6

Increased pressure stimulates aberrant dendritic cell maturation

David H Craig 1,4, Keri L Schaubert 4, Hiroe Shiratsuchi 1, June Kan-Mitchell 4, Marc D Basson 1,2,3,4,✉
PMCID: PMC6275900  PMID: 18161009

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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Abbreviations used

DC

dendritic cell

GM-CSF

granulocyte-macrophage colonystimulating factor

IL-4

interleukin-4

IL-12

interleukin-12

LPS

lipopolysaccharide

MHC

major histocompatibility complex

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