David Jackson: The Lymphatic System in Immunity and Cancer
Our lymphatic system protects us against pathogens: it collects micro-organisms and carries them to the lymph nodes where they will meet and activate T cells and B cells. Cancer cells also migrate to the lymph nodes, but instead of activating the immune system they actually suppress it. A better understanding of these mechanisms might help us better control the spread of tumours, and also block unwanted immune responses in autoimmune diseases, block tissue rejection and make vaccines more effective.
Q: What is the Lymphatic system?
DJ: The lymphatic system is basically the fluid drainage system of the body. It resembles the blood system but rather than transporting red cells in blood it transports a clear fluid called lymph. Every day about two litres of fluid leak from our blood system into our tissues and this eventually becomes lymph. The lymphatic system collects that two litres of fluid and returns it to the blood system through the veins in the neck; this prevents our bodies from becoming water-logged. And in fact in a disease called lymphoedema this is essentially what happens; when we have problems with our lymphatic system, fluid collects in the lymphs and causes this debilitating condition.
Q: Why is the Lymphatic system important for our immune system?
DJ: The lymphatic system is a sort of immune surveillance system. It protects us against pathogens. We are constantly being invaded by bacteria and viruses; we take them up through our food, we breathe them in, they get in through wounds in our skin. They must be removed by the immune system, if this didn't happen we would die. Because the lymphatic system is constantly filtering the contents of the body it collects these micro-organisms which have been engulfed by immune cells and carries them to the lymph nodes. Within the lymph nodes there are T cells and B cells which recognise these pathogens and which multiple in response. So the lymphatic system acts as a collecting system and is clearly an integral part of the immune system.
Q: What happens when cancer cells enter the lymphatic vessels?
DJ: Cancer cells spread through the lymphatic vessels. We usually think of cancer as being a single tumour that divides uncontrollably. But in fact what really happens is that cells constantly break off the main tumour and then they enter the lymphatics and spread to the lymph nodes. We probably all know someone who has had cancer and we know that when you have cancer in the lymph node it's a bad sign. Once the tumour has reached the lymph node, instead of activating the immune system in the same way that bacteria and viruses do, they actually suppress it. So cancer can actually survive within the lymph nodes and spread to distant tissues from the lymphatics.
Q: Can your research help us understand and possibly treat the spread of cancer?
DJ: Yes. Unlike other people who have been looking at the way that cancer cells trigger the division of the lymphatic vessels, proliferation of the lymphatic vessels to feed the tumour, we've been looking at how cancers actually influence the nature of the lymphatic vessels themselves. We've been carrying out molecular finger-printing of tumour lymphatics. We've identified some molecules that are up-regulated (more of them are made) in tumour lymphatics. We think that some of these molecules could be useful for anything from diagnostics to predictors of cancer outcome and perhaps even for targeting new therapies.
Q: What are the most important lines of research that have developed over the past 5 or 10 years?
DJ: I would say there are probably three or four that I can think of. The first would be the application of new microscopic imaging techniques. The development of these techniques and new models in which one can look at lymphatic vessels which are fluorescing one particular colour and then immune cells fluorescing another colour, when combined with high resolution microscopy one can actually witness the events in real time and see exactly how cells enter the lymphatics and traffic within them. The second would be probably research into molecules called chemokines which are released by lymphatic vessels and which lay down a chemical scent which then allow entry and attraction of cells into the lymphatics; I think this is going to be really important. The third would be research into growth factors that regulate the division and multiplication of lymphatic vessels: these are the factors that create new vessels in wound healing or in diseases like cancer. Obviously if we can understand how to block these growth factors or manipulate them that would be very useful. And the fourth would probably be - how did tumour cells actually suppress the immune system when they reach the lymph nodes? I think understanding this is going to be fundamental and this is a new area of research.
Q: Why does your line of research matter, why should we put money into it?
DJ: I think from what I've said you would imagine that there must be a huge drive into lymphatic research but in fact lymphatic research has been relatively neglected over the last few years and we're one of the few groups in the world that's actually trying to rectify this situation. We have been concentrating very specifically on a molecule called LYVE-1 which was discovered in my lab about 10 years ago and was one of the first molecules to discriminate between blood and lymphatic vessels so we're focusing our research on this molecule and we believe that this molecule may be involved in controlling the entry of cells into the lymphatics so it could be important both for tumour metastasis, the spread of tumours, and for the entry of immune cells and information as part of the immune response. So if we could manipulate through this molecule LYVE-1 we could perhaps block unwanted immune responses in autoimmune diseases like rheumatoid arthritis or block tissue rejection and tissue transplants or conversely we could actually potentiate traffic through the lymphatics to make vaccines more effective.
Q: How does your research fit into translational medicine within the department?
DJ: I think translational medicine is really a wide spectrum. At one end you've got basic research that's looking at the functioning of basic mechanisms and biology. And at the other end you've got research that's directed towards cures for diseases and testing new drugs. I think we've got a foot in each camp; we're looking at mechanisms controlling the entry of cells into the lymphatics. From the other side we've been working on cancer and new diagnostic techniques and developing antibodies that might block some of the mechanisms that I've spoken about. In order to develop new cures you've really got to have a foot in both camps because there's no easy answer to these questions and you can't ignore fundamental biology at the expense of clinical research. That's why I think we fit in well; we've got a foot in both camps.