Sep 21, 2021

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Eosinophils are a type of white blood cells and part of the immune system that, when functioning normally, help fight disease and infection. However, having too many activated eosinophils may contribute to disease pathology and the self-perpetuating cycle of inflammation and damage across a range of debilitating diseases.


Made in the bone marrow, they flow through the bloodstream to fight viruses, bacteria and other foreign invaders that threaten your health. When your body is in distress and a particular area is under attack, white blood cells rush in to help destroy the harmful substance and prevent illness. 


However, researchers at Tel Aviv University (TAU) have discovered a role for eosinophils that was not known. The destructive properties of proteins in these cells in the blood can be used to kill cancer cells. They can destroy the cancer cells directly, as well as recruit the immune system’s cancer-fighting T-cells.


The new study found that eosinophils help fight the battle against cancer metastases in the lungs. The researchers believe that their findings can contribute to the development of innovative approaches to cancer immunotherapy treatments, based upon the collaboration between T-cells and eosinophils. 


The study was led by Prof. Ariel Munitz and doctoral student Sharon Grisaru of the department of microbiology and clinical immunology at the Sackler Faculty of Medicine. The paper was published under the title “Metastasis-entrained eosinophils enhance lymphocyte-mediated anti-tumor immunity” in Cancer Research, a prestigious journal of the American Association for Cancer Research. 


The researchers explained the white blood cells in the immune system produce powerful destructive proteins that were originally intended for fighting parasites. However, in the modern Western world, where high levels of hygiene have significantly reduced the menace of parasites, eosinophils often have a negative impact on humans, inducing medical problems like allergies and asthma. 


Hypothesizing that the destructive power of eosinophils may prove beneficial if turned against cancer cells, the researchers initiated the current study. “We chose to focus on lung metastases for two main reasons,” said Munitz. “First, metastases and not the primary tumors are often the main problem in treating cancer, and the lungs are a major target for the metastasis of many types of cancer.  Second, in a preliminary study we showed that eosinophils collect in tumors developing in mucous tissues like the lungs, and we therefore assumed that they would be found in lung metastases as well.”


The researchers first examined human cancer tissues – biopsies from lung metastases taken from breast cancer patients. They found that the eosinophils reach the lungs and penetrate the cancer tissues, where they often release the destructive proteins that they carry. 


To examine the role of eosinophils in metastases, the researchers used an animal model. They found that lung metastases developing in the absence of eosinophils were much larger than those exposed to eosinophils. These findings led to the conclusion that eosinophils fight cancer effectively, but the question still remained: How do they do it?

“We observed that when eosinophils are missing, the tissue also lacks T-cells – white blood cells known for fighting cancer,” noted Munitz. “Consequently, we assumed that eosinophils combat cancer through T-cells. Our next task was to understand the mechanism underlying this process.” 


An extensive analysis of eosinophils found in the metastases led to two significant findings: First, in the presence of cancer eosinophils release large quantities of chemokines – substances that summon T-cells; second, these chemokines are released when eosinophils are exposed to two other substances found in the cancer’s environment, called IFN-g and TNF-a. In response to IFN-g and TNF-a, eosinophils recruit the T-cells for reinforcement. Ultimately, T-cells arriving and developing in the affected lungs slow down the growth of tumors. 


“Increasing the number and power of T-cells is one of the main targets of immunotherapy treatments administered to cancer patients today,” concluded Munitz. “In our study we discovered a new interaction that summons large quantities of T-cells to cancer tissues, and our findings may have therapeutic implications. Ultimately, our study could serve as a basis for the development of improved immunotherapeutic medications that employ eosinophils to fight cancer in two ways: on the one hand, the eosinophils will attack the cancer directly by releasing their own destructive proteins, while on the other, they will increase the number of T-cells in the cancer’s environment. We believe that the combined effect can significantly enhance the effectiveness of the treatment.”