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An American research group has discovered why cancer therapies are not always successful. They that the immune system can turn itself off in tumours by the release of long fibres. This promotes tumour growth. Targeting the fibre networks could improve cancer treatment methods.

The current study shed light on a not fully understood observation, namely that a high number of the immune cell type neutrophils within a tumour represents a poor prognosis. It appears that this is caused by a bad influence of neutrophils on T cells, which are another type of immune cells. T cells normally fight against cancer cells and destruct them. However, neutrophils within a tumour could make T cells dysfunctional. The consequence is that tumour cells are not destroyed anymore, allowing for cancer growth.

Neutrophils inactivate T cells by the release of long fibres, which are called neutrophil extracellular traps (NETs). NETs are composed of DNA and some proteins. It was already known that NETs could be a physical shield against tumour-destroying cells. The current research shows that NETs also interact with T cells directly, thereby inactivating them.

When the researchers dived into the mechanisms behind the effects of NETs on T cells, they discovered that the protein Programmed death-ligand 1 (PD-L1) is present within NETs. PD-L1 is known for its inhibitory function on T cells. The PD-L1 released by neutrophils binds to a receptor on T cells, thereby suppressing their fighting activity against cancer.

Tumour cells are not destroyed anymore, allowing for cancer growth

The scientists also found answers to the question why tumours often regrow and form metastases after surgery. They saw that operative removal of a tumour in mice stimulates neutrophils to release NETs. As could be expected from what was elucidated before, these fibre networks impair T cells. Consequently, these T cells are not able to destruct cancer cells, which allows for regrowth.

Based on all the gathered knowledge, the study team reasoned that eliminating PD-L1 during and after operative cancer treatment would prevent tumour regrowth. PD-L1 is responsible for T cell suppression, so targeting this protein would leave T cells active. Active T cells fight against remaining tumour cells. To test this idea, mice having liver cancer were operated. At the same time, the researchers administered a substance which renders PD-L1 dysfunctional. As expected, these mice had markedly less tumour regrowth and metastases formation.

Future research should determine if PD-L1 inhibition during and after tumour surgery is beneficial in humans too. A small pilot study already showed promising results. Other possibilities for the optimization of cancer treatment are the inhibition of neutrophils and the degradation of NETs. Follow-up experiments concerning this topic will contribute to a longer life expectancy of cancer patients.