Tumours evade the immune defence early on

Cancer tumours actively prevent the body's defences from taking action against them. To do this, they intervene in the development of immune cells at a surprisingly early stage. A research group led by Jan Böttcher from the Technical University of Munich has now clarified how this works in detail. Their findings could advance the development of new cancer therapies. The experts report on this in the journal "Nature".

Our organism is actually very good at fighting body cells that threaten to get out of control. Every day, it eliminates countless cells that, due to acquired mutations or epigenetic imprinting, no longer behave as they should in the tissue. For example, if they begin to proliferate excessively, the immune system switches on a suicide programme in them, "apoptosis".

Proliferating cancer tumours have found various ways to undermine the body's control mechanisms. For example, they ensure that the immune system does not recognise them as a threat. Or they paralyse the defence cells. Cancer immunotherapies are aimed at overriding these unfavourable mechanisms, shutting down the body's own defence system and thus preventing tumours from evading immune attacks. Unfortunately, these therapies do not help many patients. Experts are trying to find out why.

Stopping the tumour from maturing

Böttcher and his team have now discovered that tumours use a special messenger substance to influence immune cells at an early stage of development. Many cancer cells release the signalling substance prostaglandin E2. The substance couples to receptor molecules on stem cell-like T lymphocytes, important players in the immune system. This prevents the cells from developing into cytotoxic T cells that could attack the cancer. "The T-cell response collapses, so to speak, and the tumour can grow unhindered," explains Böttcher in a press release in which the new study is presented.

Current cancer immunotherapies start at later stages of T-cell development. This could explain why they are often insufficiently effective. Immune checkpoint inhibitors, for example, are active substances that are intended to reactivate fully developed T cells that have been paralysed by the tumour. However, if there are only a few of these cells anyway because the prostaglandin E2 has interrupted their development, the checkpoint inhibitors can only help to a limited extent. "Today's treatment approaches would probably be more effective if the effects of prostaglandin E2 on stem cell-like T cells were blocked," says Sebastian Kobold from the Ludwig Maximilian University of Munich, who was involved in the study.

A second research paper, which also appeared in "Nature", confirms these findings. The authors experimented with human tumour tissue. When they blocked the release of prostaglandin E2, the T cells multiplied more and were subsequently better able to fight the cancer cells.

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