There is evidence that the incidence of most
cancers increases with age. Recent studies have shown that specific functions
of the immune system decline with age and this may contribute to tumour
development and progression in the elderly. Dendritic cells (DCs) are immune
cells that are able to stimulate anti-tumour immune responses. However, the
effects of aging on DCs in healthy and tumour-bearing hosts are not yet
well-characterised. The aim of this study was to compare changes in DC
phenotype and function in healthy young (6–8 weeks) and geriatric (24–27
months) mice after exposure to tumour-derived factors. CD11c+ DC
proportions increased in spleens and BM of geriatric relative to young mice.
There was an organ-specific redistribution of DC subsets with age: CD8+CD4-
DC proportions increased in BM, but decreased in spleens, whilst CD4+CD8-
DCs declined in BM, but increased in spleens of geriatric mice. These data
suggest organ and subset compartmentalised changes in DCs during aging. In
vitro studies using BM-derived DCs (BMDCs) showed that unstimulated geriatric
BMDCs displayed a less activated phenotype, as shown by reduced expression of
MHC Class II, CD40 and CD54 compared to young BMDCs. Geriatric BMDC expression
of these markers was restored to the same levels as their younger counterparts
by LPS+IFNγ or IL-2+agonist anti-CD40 antibody stimulation. We simulated
conditions that occur in tumours by exposing BMDCs to conditioned media from
mesothelioma and lung carcinoma cell lines. Tumour-exposed geriatric, but not
young BMDCs, showed declining function in key compartments required for anti-tumour
activity: specifically, decreased IFNγ production and reduced ability to
stimulate CD8+ T cell proliferation. Our data suggest that DCs
exhibit compartmentalised changes with aging which can be restored with
LPS+IFNγ or IL-2+CD40 stimulation.