11 January 2017
DENDITRIC CELLS AND TUMOURS
Dendritic cells are found in tumours. The number of cells that are present can predict whether tumours are detected by the immune system and the rate at which the tumour will progress. We have observed only a small number of dendritic cells in tumours and found that the function of the cells was affected.
“Our recent work has been focussed on finding out what these tumour-associated dendritic cells do. Taking an immunotherapy approach, we used stimuli that mimic infection, because these cells are particularly sensitive to infective agents. We saw higher numbers and a wider variety of dendritic cells in the tumour. We also found that the function of the cells was enhanced, and that even if one specific type of dendritic cell was missing, the immune system could still respond to the tumour,” says Professor Ronchese.
This result suggests that treatment with an infective agent leaves a tumour with fewer opportunities to escape from the immune system. Further research is examining how metabolic factors can affect the success of this sort of immunotherapy.
Although dendritic cells are rare, they are also very powerful, causing the immune system to be activated inappropriately and resulting in inflammatory diseases such as allergic inflammation.
“Our previous research found that the immune system is able to control or suppress the function of dendritic cells. We are now working to develop vaccines that can activate this ‘control’ arm of the immune response so we harness it to help treat inflammatory diseases.”
Professor Ronchese says the vaccines can be very effective in some cases and less so in others, so the next step is to refine them to produce more consistent activity.
Dendritic cells are also involved in allergic sensitisation – the immune system’s first exposure to an allergen such as dust mites, pollen or a chemical. To better understand the sensitisation process, Professor Ronchese and her team are studying the genetic changes in the transcriptome (all the molecules of RNA rather than DNA) of dendritic cells, using bioinformatics, a powerful computing technology.
The genes that were activated and then expressed RNA after being exposed to two allergens (the chemical dibutyl phthalate and a parasitic worm) were tracked in a model of allergy.
“We assumed that because both sensitisation methods cause allergy, we would see similar things going on in the transcriptome, but in fact there is very little in common. We found RNA coding for molecules we did not suspect were involved in allergies, as well as a lot of differences between the two sensitised groups,” she says.
Only a handful of genes from many hundreds of possibilities appeared in both cases. Interestingly this package of genes is also found in other cells (like T and B cells) that mediate allergies, but their role in dendritic cells is not yet understood. The genetic changes in response to the chemical allergen were relatively simple but much more complexity was observed for the parasitic worm.
Prof Ronchese would like to acknowledge the support of the Hugh Green Foundation for the cell sorting technology, which she says has been absolutely critical for this work.
Professor Franca Ronchese
Dr Camille Baey, Dr Emmanuelle Cognard, Dr Lisa Connor, Dr David Eccles, Connie Gilfillan, Kerry Hilligan, Evelyn Hyde, Dr Olivier Lamiable, Dr Sotaro Ochiai, Sam Old, Dr Deepa Patel, Dinindu Senanayake, Shiau Choot Tang, Kirsty Wakelin, Ruby White, Dr Mark Yang