T cells are a type of lymphocyte, one of our white blood cells that is part of our immune system. T cells take part in the specific immune response - a process that kicks in if a pathogen gets into the body and starts an infection. There are different types of T lymphocytes that carry out the cellular response: helper T cells and cytotoxic (killer) T cells. Helper T cells coordinate the action of B cells, phagocytes and cytotoxic (killer) T cells, whilst cytotoxic (killer) T cells attack and kill:

• host cells that have been infected with a pathogen, like a virus
• cells from other organisms of the same species, like transplanted tissue
• abnormal body cells, like those in a tumour

In the destruction of tumour cells, cytotoxic T cells can bind to specific tumour-specific antigens presented on the surface membrane of the tumour cell – antigen presentation. The cytotoxic (killer) T cell then releases perforin and granzymes. Perforin makes tiny holes in the cell surface membrane of the tumour cell and granzymes trigger apoptosis (programmed cell death) and kill the tumour cell.

Cancer immunotherapy is a treatment that supercharges our own immune response using cytotoxic (killer) T cells. An unfortunate side effect of come cancers is that they can hide from our T lymphocytes and even turn them off. With immunotherapy, T cells are back in action. But one problem that can occur is T cell exhaustion which stops them being active and the treatment stops working.

Scientists have now found the solution to keeping these cells going on longer and not becoming exhausted. As T cells encounter tumour cells they respond by producing cytotoxic (cancer-killing) proteins. Protein synthesis is a metabolically demanding process – it needs a lot of ATP. The scientists discovered that this protein synthesis is controlled by a signal molecule called MEK. When MEK activity becomes too high, it causes T cell exhaustion. A MEK inhibitor could be the solution to allow cells to balance the energy demands of making cytotoxic proteins and the energy available to them. So, they can stay active and continue to kill tumour cells. In other words, it allows the cell to better regulate it’s ATP fund and how ATP is spent – the energy currency of the cell.

This does mean that when MEK is inhibited that fewer cytotoxic proteins are made but better to have a slower but longer lasting response rather than a short but powerful one that ends in T cell exhaustion.

It all comes back to cells and understanding T cell biology has been critical to this study for the development of more successful cancer treatments.

Download the article from the Science Daily page here