How does neuroblastoma evade immune cells?
✤ Neuroblastoma is a rare type of solid tumour that affects infants and very young children. It grows from nerve cells left over from development in the womb
. Normally these cells vanish once they have done their job, and the reasons why they persist and carry on dividing in rare instances to become a cancer remain a mystery.
✤ One of the intriguing features of neuroblastoma is that the tumour creates an environment where the immune system is suppressed
. Cancer cells often send out molecules to suppress the immune system, so that they can remain undetected within our bodies.
✤ Which is why immunotherapies, that can 'wake up the immune system', have so much promise. But first, we have to understand exactly how cancer cells suppress the immune system
, so that we can develop those new immunotherapies.
✤ Our immune system is made up of many different types of cells. The most important is type of cell is known as a T-cell. T-cells can act as the soldiers of the immune system
, actively engaged in ‘search and destroy’ missions looking for harmful disease-causing enemy cells. Unfortunately cancer cells can ‘hide’ from T-cells
by sending out molecules that put these T-cells to sleep, through a process known as immunosuppression.
✤ But what are these molecules, and how do they cause immunosuppression? And most importantly, how can we exploit this knowledge to develop therapies that can re-activate these T cells?
✤ Researchers at the University of Birmingham have found that a molecule called arginine
might be involved. Arginine is an amino acid normally found within our cells
, and is broken down by an enzyme called arginase. The team discovered that neuroblastoma cells produce a lot
of arginase enzyme. It means that in the environment surrounding neuroblastoma cells, known as the tumour microenvironment, arginine levels are very low
. This reduced level of arginine is involved in the immunosuppression seen in neuroblastoma tumours. The team also showed that this same mechanism might be involved in immunosuppression in another childhood cancer, called acute myeloid leukaemia (AML).
✤ So what is the impact of this research? We now know how important it is to regulate arginine levels in the tumour
, so that T-cells can remain active. This immunosuppression also affects cell-based therapies, where engineered T cells are injected into patients. So it’s even more important that we make sure that the immunosuppressed tumour microenvironment is addressed before trying out new immunotherapies for treatment.
✤ It is tempting to think of giving arginine supplements to patients, to 'boost their immune system', but there is concern that it might feed tumour growth. A better approach would be to inhibit the activity of the enzyme, arginase
. Excitingly, there are several compounds that act on arginase that are going through pre-clinical investigations. When given in combination with existing immunotherapies, these arginase inhibitors could greatly enhance treatment, and so improve patient outcome for the cancers where they work
Full paper: http://cancerres.aacrjournals.org/content/75/15/3043.long
Image credit: Neuroblastoma cell line, Wikipedia (https://en.wikipedia.org/wiki/Neuroblastoma#/media/File:BiggeggSH-SY5Y.jpg