A new method for treating colon cancer by strengthening the immune system

Researchers at Tel Aviv University: white blood cells of the eosinophil type play an important role in eliminating malignant cells of colon cancer * eosinophils are cells of the immune system known to cause allergies and asthma; The new study examined for the first time their connection to cancer * The article was published in the journal Cancer Immunology Research 

Researchers in the laboratory of Prof. Ariel Munitz from the Department of Clinical Microbiology and Immunology at the Tel Aviv University School of Medicine examined for the first time the relationship between cancer and cells of the immune system called eosinophils. The researchers found that eosinophils play an important role in eliminating malignant cells of colon cancer. Based on their findings, they are now offering a number of innovative and ground-breaking approaches for immunological treatment of cancer patients.

The research was carried out by PhD student Hadar Reichman from Prof. Munitz's laboratory, in collaboration with the gastro department at the Ichilov Hospital. The article was published last night (21.1.19) in the journal Cancer Immunology Research.

"Eosinophils are white blood cells of the immune system, which secrete strong destruction proteins, and their role in evolution is to fight parasites," explains Prof. Munitz. "But in the modern western world, when hygiene is high and parasites are few, they often become a negative factor, causing allergies and asthma. We believed that the ability of eosinophils to fight parasites and wreak havoc may be a positive factor if the destruction is directed towards cancer cells. Therefore, we asked to investigate their connection to cancer - an aspect that has hardly been investigated to date."
According to Prof. Munitz, eosinophils are mainly concentrated in mucous tissues in the body, which come into contact with the outside world - such as the respiratory and digestive systems, and the urinary and sexual systems, and their largest reservoir is found in the digestive system. Therefore, the researchers decided to concentrate on colon cancer. In the first stage, they took samples from the tumors of 275 patients, and checked if there was a relationship between the number of eosinophils in the tumor and the severity of the disease.

"We discovered that the more eosinophils there are in the tumor, the less serious the disease," says Prof. Munitz. "Does this mean that eosinophils fight and damage cancer? We decided to test this in mice, in different models of colon cancer. First, we found that the cancerous environment invites these cells to it, and they are able to actually infiltrate the tumors and even live inside them for a long time. What's more: mice engineered to have no eosinophils at all developed a much larger number of tumors than mice with eosinophils, and died in a shorter time; And vice versa, mice

Engineered to have more eosinophils, developed fewer tumors compared to normal mice. The conclusion: eosinophils have a role in inhibiting the progression of colon cancer in mice."
In the next phase of the study, eosinophils from humans and mice were placed in test tubes in the laboratory, with colon cancer cells next to them, and it turned out that the eosinophils indeed destroy the cancer cells with the highest efficiency. Genetic sequencing of eosinophils taken from cancerous tumors, compared to eosinophils from healthy intestines, revealed that eosinophils from the tumors have a unique genetic signature, indicating increased activity.
"The meaning is, apparently, that the eosinophils in the tumor react to substances in their environment, which cause them to secrete an especially large amount of proteins capable of killing cancer cells," says Prof. Munitz. "In a careful analysis of the eosinophils, we discovered that they respond specifically to a protein called interferon gamma, and we concluded that it is probably responsible for increasing their activity. Indeed, adding interferon gamma to the test tubes greatly intensified the killing activity of the eosinophils against the cancer cells."
Also, in an examination of cancerous tumors removed from mice, as well as in human tumors, clusters of eosinophils were discovered next to dead cancer cells after they had released some of their killing proteins - a sign of significant anti-cancer activity. Another important finding is that the anti-cancer activity of the eosinophils is completely independent, and there is no connection between it and that of the T-type white blood cells, which are known as cells whose role is to fight cancer, and are currently a major target for immunotherapy treatments.

"In fact, we discovered a new target for immunotherapy treatments for cancer patients - the eosinophils," Prof. Munitz concludes. "We hope that our research will serve as an infrastructure for drug development in a number of different approaches: substances that will recruit more eosinophils to the tumor environment, substances that will increase the activity of the eosinophils that are already in the tumor environment, as well as combined treatments that will connect eosinophils to T cells, thus strengthening the effectiveness of the treatment. In my laboratory we are currently working on all these aspects, and are trying, among other things, to identify the particular protein secreted by the eosinophils, which kills the cancer."
The research was funded by the Cancer Society, the Israel Cancer Research Fund and the National Academy of Sciences.