To fight infections and heal wounds, immune cells must enter the tissues. They must also invade tumors to fight them from the inside. Scientists from the Siekhaus group at the Institute of Science and Technology (IST) in Austria have now discovered how immune cells protect their sensitive interiors as they squeeze between cells in tissue. With their study published in the journal PLOS Biology, the team is laying the foundations for the identification of new targets in the treatment of cancer.
It is difficult to know when exactly immune cells will try to invade a tumor. In order to be able to study this cell invasion process in detail, scientists like Professor Daria Siekhaus and her team need something more reliable. That’s why they turn to fruit fly embryos. During the development of these embryos, macrophages, the dominant form of fruit fly immune cells, travel from where they were born to where they are needed to invade tissue. They do so at a certain point in time, allowing scientists to study the process within these tiny, transparent animals. With the help of IST Austria’s state-of-the-art bio-imaging facility, they watch macrophages – labeled with a green fluorescent protein – make their way into tissue.
Creation of armor
What cellular changes are needed for this and which genes trigger such alterations are still largely unknown. With their new study by early authors Vera Belyaeva, Stephanie Wachner and Attila Gyoergy, the Siekhaus group sheds light on this process, essential in health and disease. âPreviously, we found out that a specific gene, called Dfos, is enriched in immune cells and we wondered what it was doing,â says Siekhaus.
“Now we can prove that it triggers actin filament assembly.” These protein strands are concentrated inside the cell membrane, also known as the cell cortex, giving the cell surface stability. Scientists show that through a complex cascade involving different proteins, actin filaments are made denser and more connected to each other, forming a stable shell. “We hypothesize that it functions as a reservoir, deforming surrounding cells while protecting the nucleus of the immune cell from mechanical pressure as it invades tissue,” says Siekhaus. In addition, the team was able to show in vivo that the absence of this actin shell makes it more difficult for immune cells to infiltrate unless the surrounding tissue is made softer.
Strengthen immune cells to fight cancer
Although a fruit fly and vertebrates such as mice and humans may not have much in common at first glance, there are many similarities in how their genes work. In collaboration with Prof. Maria Sibilia from the Medical University of Vienna, researchers at IST Austria have found evidence that the vertebrate Fos gene, the equivalent of the fruit fly gene Dfos, activates the same pathways genetic. “We believe that the same mechanism that we found in the fruit fly also plays a role in vertebrates,” says biologist Daria Siekhaus.
This gives hope that the group’s findings could help identify new targets for cancer treatment. In the field of immuno-oncology, researchers are looking for ways to activate the body’s immune system to attack a tumor. One of the challenges they face is allowing immune cells to infiltrate the tumor.
If we could strengthen their protective envelope, it would make it easier for them to invade tumor tissue. “
Professor Daria Siekhaus, IST Austria