Dr Marek Wagner, head of the Innate Immunity Research Group at Łukasiewicz – PORT, has achieved something that does not happen very often in Polish (and not only) science, but is the dream of every researcher. He has just published an article in “Nature”, one of the most prestigious scientific journals in the world. In it, he described, among other things, the results of his research on ILC2 immune cells, demonstrating that cells hitherto known to induce type 2 immune responses associated with protection against parasites may also play a key role in the fight against cancer.
ILC2 cells – a discovery that changes the perspective
- Two moments are important in this story. The first is when ILC2 cells, or innate lymphoid group two cells, were discovered by Japanese researchers in 2010. They found them in the fatty tissue of the mesentery, an organ that supports and stabilises the internal organs of the abdominal cavity, and noted that they protect the body from parasitic worms such as roundworms and flukes. Today, we already know that these cells are found in all barrier tissues, i.e. skin, lungs and intestine, among others, protecting the human body from pathogens.
How is it possible that we are born with them and no one has discovered them before? – ILC2 cells, despite being lymphocytes, behave slightly differently. Typical T and B lymphocytes have receptors on their surface that recognise specific molecules, antigens, present on the surface of pathogenic microorganisms and tumour cells. Based on these, they trigger an immune response. ILC2 cells do not have these receptors, which is why they remained undiscovered for so long when studying the body’s defence mechanisms, dr Wagner explains.
At the time of publication of the Japanese researchers’ discovery, the scientist was conducting research into the role of adipose tissue in melanoma development in Boston.
- The results of my study suggested that a large number of macrophages are present in the adipose tissue located in close proximity to the cancerous tumour, which in turn stimulate tumour growth by inducing the development of blood vessels. The discovery of ILC2 cells in adipose tissue inspired me to research their role in cancer development. My initial assumption - actually, it was not just me, the entire scientific world thought so at the time - was that the presence of ILC2 cells stimulated an increase in the number of macrophages and thus tumour growth. And with this idea, I flew to Japan.
New insights into innate immunity
- The conducted experiments did not confirm my original hypothesis. What's more - I have not been able to locate these cells in the tumour. That is when a revolutionary hypothesis that ILC2 cells could inhibit cancer tumour growth occurred to me. This initiated a series of experiments that confirmed that ILC2 cells inhibit melanoma growth. Today there is no doubt about it
The scientist, who is now continuing his research at Łukasiewicz – PORT, admits that the first results of his research have caused considerable controversy.
- I was told that this was impossible, that the exact opposite was true, because at the same time other researchers were showing that these same cells support the development of breast cancer, for example.
In melanoma, ILC2 cells produce cytokines, or protein messengers, in response to tumour growth. One of these, interleukin 5, mobilises eosinophils, cells of the immune system that show the ability to destroy cancer cells. It is – in a nutshell – a mechanism that, in the case of this cancer, acts as a natural line of defence, innate and immediate.
However, ILC2 cells do not always work in this way. In the case of breast cancer, their presence may stimulate the creation of a tumour-promoting environment through the recruitment and activation of macrophages. It all probably depends on the type of tumour, the microenvironment in which it develops, the interaction with other cells in the tumour (and there are not only cancer cells there, but also immune cells and many others). – And this is precisely what makes ILC2 cells both fascinating and difficult to understand, adds dr Wagner, who, together with his Innate Immunity Research Group, is now focusing on better understanding the mechanisms of action of these cells.
ILC2 cells – an evolutionary defence mechanism
ILC2 cells are the proof how evolution has adapted our immune system to fight threats.
- Their original role was to protect us from parasites, i.e. foreign organisms entering our body and causing havoc in it. In order to deal with them, these cells activated eosinophils, stimulated mucus production in the gut, enhanced peristaltic movements and triggered other mechanisms to eliminate parasites from the body.
In today’s world, where we rarely come into contact with parasites, and even if we do – there are very effective anti-parasitic drugs – our cells have had to find a new task for themselves. – Melanoma, like most cancers, acts in a parasite-like manner. Cancer cells spread and devastate our body just like parasites.
The mechanism of action of ILC2 cells – as dr Marek Wagner proves in a paper recently published in “Nature” – has remained the same, but evolutionarily adapted to the new needs of the organism and the target it attacks has changed.
Melanoma – an avalanche of cases in Poland
In the last three decades, the incidence of melanoma in Poland has increased by as much as 300%. This constitutes the result of a lack of adequate prophylaxis and increased exposure to ultraviolet radiation during more frequent trips to warm countries. But it is also a result of climate warming – we are spending more and more sunny days outside.
In the first stage, melanoma has a fairly high cure rate, but subsequent stages are more resistant to treatment. – While there are immunotherapies, they are not 100% effective and do not work in every patient. Moreover, they have severe side effects,” says a researcher from Łukasiewicz – PORT – and adds that there is still much to be explored, but the potential for anti-tumour activity of the type 2 immune response is significant.
- There is no doubt that we need to look for new forms of anti-cancer therapies. That is why we look at every piece of information that brings us closer to learning about cancer and how we can fight it with great hope. We believe that the research we are conducting could lead to new diagnostic and therapeutic tools in oncology.
