Natural Killer cells
The Molecular and Cellular Immunology Laboratory at the Leeds Institute of Molecular Medicine are investigating the action of a group of white blood cells known as Natural Killer cells. These killer cells are part of the immune system. There is a lot known about how the immune system helps to combat infections, such as the common cold or ‘flu. In recent years, it has been discovered that the immune system can also detect cancer cells and kill them. This has led to the prospect of designing new treatments to boost the activity of these cells in patients.
Two research projects in this area have been funded by Candlelighter’s and have recently been published in the Journal of Immunology. Tim Holmes was awarded the Danny Freeman Candlelighter’s studentship to investigate how these killer cells can detect and destroy Ewing’s sarcoma family tumours, a cancer that occurs in teenagers and young adults. “Ewing’s sarcoma cells cultured in the laboratory are easily destroyed by these killer cells” said Tim Holmes, “but this was puzzling, because in patients the cancer is resistant to the immune system”. However, when the cancer cells were cultured as 3D structures, which more closely resemble the tumours seen in patients, the cancer became highly resistant to the killer cells. “For the first time we are able to see how the structure of a tumour might alter its ability to be recognised by the immune system”, said Dr. Holmes. Most importantly, Dr. Holmes found that a group of immune hormones known as cytokines were able to boost the killing of the Ewing’s sarcoma cells in the lab. These cytokines are used in the treatment of other cancers and this research suggests that similar treatments might be beneficial in Ewing’s sarcoma patients. Dr. Holmes added “We were able to identify some of the molecules used by the cancer to resist the attack by the killer cells, we believe that these molecules might be important in other cancers too”. The techniques developed in this study are now being used to develop improved laboratory models for the investigation of potential therapies in Ewing’s sarcoma and other cancers.
In a separate project funded by Candlelighter’s, Dr. Josie Meade, apost-doctoral research fellow in the group, has investigated how these whiteblood cells actually kill cancer cells.“We were interested in investigating the activity of a molecule calledperforin. Alterations in this gene causean important childhood blood disease known as FHL and can also lead to bloodcancers in some patients” said Dr. Meade.Dr. Meade studied the biochemical pathways that lead to the activationof this molecule in the killer cells, she added, “the perforin molecule forms apore that helps to punch holes in the cancer cells. We found that perforin needs to be switchedon by other molecules in the killer cells, a little like releasing ahandbrake”. Dr. Meade found thatperforin is activated as the killer cells develop in the bone marrow. She added, “surprisingly, we found thatperforin is switched on by a different mechanism to other killer cell proteinswe have studied in the past, this helps to explain why this disease is moresevere”. A group of FHL patientspreviously studied in Leeds may hold the clue.“We have identified an enzyme in the killer cells which can switch onperforin, the disease looks like it can be caused either by problems inperforin itself, or in the switch”.
The researchgroup leader, Dr. Graham Cook, added “these advances would not have beenpossible without support from Candlelighter’s.We are very grateful for all of the hard work put in by theCandlelighter’s fundraisers. The more weunderstand about the ways in which these cancers and immune cells interact, thebetter our chances of revealing new ways to treat these diseases”.
Dr. Josie Meade,Dr. Graham Cook and Dr. Tim Holmes.