Dr. Marek Wagner’s Publication in Nature

Dr. Marek Wagner, head of the Innate Immunity Research Group at Łukasiewicz – PORT, has achieved something that is rare in Polish (and not only Polish) science, and a dream for every scientist. He has just published an article in Nature, one of the most prestigious scientific journals in the world, in which he described, among other things, the results of his research on ILC2 immune cells, showing that cells previously known for inducing a type 2 immune response associated with protection against parasites can also play a key role in the fight against cancer.

ILC2 Cells – A Discovery that Changes the Perspective

“There are two key moments in this story,” says Dr. Marek Wagner. “The first is the discovery of ILC2 cells, or innate lymphoid cells of group 2, by Japanese scientists in 2010. They found them in mesenteric adipose tissue, the tissue that supports and stabilizes the internal organs of the abdomen, and noticed that they 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 these cells, yet no one had discovered them before? “Although ILC2 cells are lymphocytes, they behave a little differently. Typical T and B lymphocytes have receptors on their surface that recognize specific molecules, antigens, present on the surface of pathogens and cancer cells. Based on these receptors, 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 defense mechanisms,” explains Dr. Wagner.

When the Japanese researchers published their discovery, Dr. Wagner was conducting research on the role of adipose tissue in melanoma development in Boston.

“My research results suggested that in the adipose tissue adjacent to a tumor, there is a large number of macrophages, which, in turn, stimulate tumor growth by inducing angiogenesis. The discovery of ILC2 cells in adipose tissue inspired me to investigate their role in cancer development. Initially, I hypothesized— and so did the entire scientific community at the time—that the presence of ILC2 cells stimulates an increase in macrophages, and thus tumor growth. That’s the idea I took with me to Japan.”

New Insights into Innate Immunity

“The experiments I conducted did not confirm my initial hypothesis. Moreover, I was unable to locate these cells in the tumor. That’s when I came up with the revolutionary hypothesis that ILC2 cells may inhibit tumor growth. This led to a series of experiments that confirmed that ILC2 cells inhibit melanoma development. Today, there is no doubt about this,” says the scientist, who is currently continuing his research at Łukasiewicz – PORT. He acknowledges that the initial results of his research caused considerable controversy. “I was told it was impossible, that it was exactly the opposite, because, at the same time, other scientists were showing that these same cells promote the development of breast cancer, for example.”

In the case of melanoma, in response to tumor development, ILC2 cells produce cytokines, which are protein messengers. One of these cytokines, interleukin 5, mobilizes eosinophils, which are immune cells capable of destroying cancer cells. This, in a simplified manner, is the mechanism that acts as a natural, innate, and immediate line of defense against this cancer.

However, ILC2 cells do not always act in this way. In the case of breast cancer, their presence may promote the creation of a tumor-supportive microenvironment by recruiting and activating macrophages. It likely depends on the type of cancer, the microenvironment in which it develops, and interactions with other cells in the tumor (which contains not only cancer cells but also immune cells and many others). “And that is what makes ILC2 cells both fascinating and difficult to understand,” adds Dr. Wagner, whose Innate Immunity Research Group is now focused on better understanding the mechanisms of these cells.

ILC2 Cells – An Evolutionary Defense Mechanism

ILC2 cells are proof of how evolution has adapted our immune system to fight threats. “Their primary role was protection against parasites—foreign organisms entering our bodies and causing havoc,” explains Dr. Wagner. “To deal with them, these cells activated eosinophils, stimulated mucus production in the intestines, strengthened peristaltic movements, and initiated other mechanisms to eliminate the parasites from the body.”

In today’s world, where we rarely encounter parasites (and even when we do, there are very effective antiparasitic drugs), our cells had to find new tasks. “Melanoma, like most cancers, acts in a way similar to parasites. Cancer cells spread and ravage our body just like parasites do.”

The mechanism of ILC2 cell action— as Dr. Marek Wagner demonstrates in his article published in Nature— remains the same, but it has evolved to meet the new needs of the body and changed the target it attacks.

Melanoma – A Surge in Incidence in Poland

Over the past three decades, the incidence of melanoma in Poland has increased by as much as 300%. This is due to the lack of adequate prevention and increased exposure to ultraviolet radiation from more frequent trips to warmer countries. However, it is also a result of climate change  — we spend more and more sunny days outdoors.

In the early stages, melanoma has a high cure rate, but later stages are more resistant to treatment. “There are, of course, immunotherapies, but they are not 100% effective and do not work for every patient. Additionally, they have significant side effects,” says the scientist from Łukasiewicz – PORT. He adds that much remains to be studied, but the potential for type 2 immune responses to play an anti-cancer role is significant.

“There is no doubt that we need to search for new forms of cancer therapy. That’s why we view any information that brings us closer to understanding cancer and fighting it with great hope. We believe that the research we are conducting can lead to the development of new diagnostic and therapeutic tools in oncology.”