Dr. Marek Wagner, Head of the Innate Immunity Research Group at Łukasiewicz – PORT, has achieved something that is rare in Polish science (and beyond) and a dream of every scientist. He has just published an article in Nature, one of the most prestigious scientific journals in the world. In the paper, he presents, among other findings, the results of his research on ILC2 immune cells, demonstrating that cells previously known mainly for inducing 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 perspective
– There are two key moments in this story – says Dr. Marek Wagner. – The first is the discovery of ILC2 cells, or group 2 innate lymphoid cells, by Japanese scientists in 2010. They identified them in mesenteric adipose tissue, an organ that supports and stabilizes the internal organs of the abdominal cavity, and observed that these cells protect the body against parasitic worms such as roundworms and flukes. Today we know that these cells are present in all barrier tissues, including the skin, lungs, and intestines, where they protect the human body from pathogens.
How is it possible that we are born with them and yet they remained undiscovered for so long?
– Although ILC2 cells are lymphocytes, they behave somewhat differently. Typical T and B lymphocytes have surface receptors that recognize specific molecules—antigens—present on pathogens and cancer cells, which trigger an immune response. ILC2 cells lack these receptors, which is why they remained undetected for so long in studies of immune defense mechanisms – explains Dr. Wagner.
At the time the Japanese researchers published their discovery, Dr. Wagner was conducting research in Boston on the role of adipose tissue in melanoma development.
– My results suggested that adipose tissue located in close proximity to a tumor contains a large number of macrophages, which in turn stimulate tumor growth by inducing blood vessel formation. The discovery of ILC2 cells in adipose tissue inspired me to investigate their role in cancer development. Initially, I assumed—like much of the scientific community at the time—that the presence of ILC2 cells would stimulate macrophage accumulation and thus promote tumor growth. With this hypothesis, I went to Japan.
A new view on innate immunity
– The experiments did not confirm my original hypothesis. What is more, I was unable to locate these cells within the tumor. That is when a revolutionary idea emerged—that ILC2 cells might actually inhibit tumor growth. This marked the beginning of a series of experiments that confirmed ILC2 cells suppress melanoma progression.
Today, there is no doubt about this, although the scientist—who now continues his research at Łukasiewicz – PORT—admits that his initial findings sparked considerable controversy.
– I was told this was impossible and that the opposite must be true, because at the same time other researchers were showing that the same cells support, for example, the development of breast cancer.
In melanoma, in response to tumor development, ILC2 cells produce cytokines—protein signaling molecules. One of them, interleukin-5, mobilizes eosinophils, immune cells capable of destroying cancer cells. This—put simply—is a mechanism that in melanoma acts as a natural line of defense, innate and immediate.
However, ILC2 cells do not always act in this way. In breast cancer, their presence may stimulate the formation of a tumor-promoting environment through the recruitment and activation of macrophages. Everything likely depends on the type of cancer, the tumor microenvironment, and interactions with other cells within the tumor—not only cancer cells, but also immune cells and many others.
– And this is precisely what makes ILC2 cells both fascinating and difficult to understand – adds Dr. Wagner, whose Innate Immunity Research Group is now focused on gaining a deeper understanding of the mechanisms governing these cells.
ILC2 cells – an evolutionary defense mechanism
ILC2 cells are evidence of how evolution has adapted our immune system to combat threats.
– Their original role was protection against parasites—foreign organisms that invade our bodies and cause destruction – explains Dr. Wagner. – To deal with them, these cells activated eosinophils, stimulated mucus production in the intestines, enhanced peristaltic movements, and triggered other mechanisms that eliminated parasites from the body.
In today’s world, where contact with parasites is rare—and when it does occur, highly effective antiparasitic drugs are available—these cells have had to find new functions.
– Melanoma, like most cancers, behaves in a way similar to parasites. Cancer cells spread and devastate the body in much the same way.
As shown by Dr. Marek Wagner in the article just published in Nature, the mechanism of action of ILC2 cells has remained the same, but through evolution it has adapted to new needs of the organism—the target has changed.
Melanoma – a dramatic increase in incidence in Poland
Over the past three decades, the incidence of melanoma in Poland has increased by 300%. This is the result of insufficient prevention and increased exposure to ultraviolet radiation due to more frequent travel to warm countries. It is also an effect of climate change—we spend more and more sunny days outdoors.
In its early stage, melanoma has a relatively high cure rate, but later stages are far more resistant to treatment.
– There are immunotherapies available, but they are not 100% effective and do not work for every patient. Moreover, they can have severe side effects – explains the scientist from Łukasiewicz – PORT, adding that there is still much to be studied, but the anticancer potential of type 2 immune responses is significant.
– There is no doubt that we must seek new forms of anticancer therapies. That is why we view every piece of information that brings us closer to understanding cancer and how to fight it with great hope. We believe that the research we are conducting may lead to the development of new diagnostic and therapeutic tools in oncology.
