New research published in the journal Immunity, has revealed that the monocyte-derived dendritic cells are not identical descendants, but rather a very diverse mixture. The finding is important for the further development of tailor-made immunotherapies for combating tumour cells.

When the immune system mobilizes its troops, antigen-presenting cells play an important role. They can emerge from white blood cells (monocytes) that circulate in the blood. Monocyte-derived dendritic cells (moDCs) have been obtained from patients' blood for immunotherapy to treat various cancers, for example, melanoma, lung or colon cancer.

It was assumed that the therapeutically used cells are identical to dendritic cells. Dendritic cells have become known as the most potent antigen-presenting cells. They recognize foreign structures of invaders, pick them up and present them to other immune cells to strengthen the targeted defence.

Only a small proportion of patients respond to therapy with moDCs, whilst very little effect is seen in the vast majority of patients. Using the latest high-tech methods, the researchers team studied the properties of these special cells.

The scientists extracted monocytes which they transformed into a large variety of antigen-presenting cells using human blood and analyzed using state-of-the-art methods. It became clear that there is a huge variety of moDCs.

Using state-of-the-art computer-assisted models, they showed that moDCs differ from dendritic cells and present a mixture of cells with very diverse properties and functions, explains lead author Jil Sander from the LIMES Institute.

MoDCs have an extraordinarily large plasticity, enabling them to tailor their response to pathogens, tumours or endogenous danger signals. This ability is fine-tuned by specific gene regulation, adds second lead author Dr Susanne V. Schmidt. They most closely resemble immune cells that occur in inflammation.

The wide variety of different moDCs could explain why moDCs activate the immune system against the tumour cells only in some patients. The study results are the basis for tailoring moDCs for the patients, thereby significantly improving cancer immunotherapy, says Prof. Schultze from the LIMES Institute.

Additionally, the research team achieved important results for basic research. The time aspect had been largely ignored so far in the differentiation of monocytes. Depending on how long the substance, for example, interleukin 4, acted on the cells, the moDCs could be very different. The researchers agree that the potential of monocyte-derived dendritic cells is underestimated.