Why doesn’t the immune system work against Brain Cancer?

Why doesn’t the immune system work against Brain Cancer?

That is a VERY good question. Why would the body allow tumour cells to grow and destroy the normal brain? Isn’t the immune system supposed to rid us of foreign and destructive material?

The immune system certainly is supposed to do this. It a highly evolved and finely tuned system that in general works extremely well. There are checks and balances built into this system which can go wrong – it can be overactive in some people who develop autoimmune diseases such as Multiple Sclerosis (MS). It can be deficient and allow infections to develop when normally they would be cleared.

When brain cancer develops, the immune system does recognize the tumour cells and makes some attempts to react to it. The problem is that that reaction is nowhere near strong enough, and the tumour itself develops mechanisms to damp down and avoid the immune response. There are many ways this happens.

One way the tumours appear to do this, is by causing immune cells to die if they enter the tumours space. Ingenious right – but we don’t want this to happen. In fact this is why many of the immunotherapies tried so far have not worked very well. A recent paper published in the Journal “NeuroOncology”:

Immunosuppressive tumor-infiltrating myeloid cells mediate adaptive immune resistance via a PD-1/PD-L1 mechanism in glioblastoma (Antonios et al.) (2017) has further clarified this situation. It appears that some immune cells within the tumour actually suppress the effective anti-tumour response, by expressing a molecule called PD-L1. If this molecule is blocked using an antibody drug, then immunotherapy may be much more effective. These drugs are currently available and in use in some cancer patients, such as for melanoma. One of these is known as Pembrolizumab (Keytruda).

Our group has demonstrated some effectiveness of immunotherapy in brain cancer, specifically using adoptive T cell therapy. We would also love to combine our therapy with drugs such as Pembrolizumab. When I approached the company (MERCK) that sells this drug to see if they could help our research, they were not interested!!!

If was a disappointing response to say the least. We will try them again and see what they say……

-By Prof David Walker