Our Immune Systems Can Be Used to Battle Against Cancer

When you are at war in your land against an aggressor who attacks you, you shall sound short blasts on the trumpets, that you may be remembered before Hashem your God and be delivered from your enemies. Numbers 10:9 (The Israel Bible™)

Unknown to us all, there is a battle raging constantly in our bodies every minute. Our immune system – consisting of macrophages, neutrophils, dendritic cells, natural-killer cells, neutrophils, mast cells, basophils and B cells in the blood – is a biological machine aimed at protecting us from invaders.

These cells aim to kill bacteria or viruses and defend our bodies against disease and infection, storing data about these pathogens so they can identify and attack them again should they launch another attack.

But how about cancer – cells that undergo mutations and grow uncontrollably? There is an enduring debate on whether a main function of the immune system is to prevent cancer. The concept of immunological surveillance of cancer was developed by Lewis Thomas and Frank Macfarlane Burnet more than half-a-century ago.

Experts maintain that if none of us had an immune system, we would all get cancer. Fortunately, this doesn’t happen, but some of us do get one or more of this fearsome collection of diseases.

The immune system can help to fight cancer. Some cells of the immune system can recognize cancer cells as abnormal and kill them. Unfortunately, this may not be enough to get rid of a cancer altogether.
But some new treatments aim to use the immune system to fight cancer.

When it comes to cancer, the protective army sent by our immune system doesn’t always win the battle. Oncologists say that the immune system filters out a small number of cancer cells to prevent us from having visible cancer in the body. Yet, as time passes, that delicate balance can fail because the immune system is overpowered by aggressive cancer cells that it fails to detect and fight.

Among the ways that the immune system can fight tumors is non-specific immune stimulation. This makes it possible for the body to stimulate an immune response in general way. Certain drugs and other treatments are given to increase their immune response.

Another weapon is T cells, which are taken from the patient and processed – or grown – in the lab and then returned to the patient.

Yet another technique is making immune checkpoint inhibitors. This keeps T-cells inactive until needed, preventing them from harming normal cells. There are drugs that block the checkpoints, freeing them so they can attack the cancer.

Unfortunately, these techniques don’t succeed in every patient and can even cause serious side effects. Cancer researchers around the world are working hard on studying these processes to improve immune therapy for all patients.

As the researchers learn more about how cancer tries to evade the immune system and some immune cells even help tumors grow, there is hope that they will develop new strategies to help this biological machine to fight malignancies.

More than 200,000 Israelis alone are struggling with types of cancer, and every year, 29,000 more are diagnosed. Now, a group of senior researchers from Harvard Medical School, with the participation of a team from Bar-Ilan University in Ramat Gan, near Tel Aviv, has discovered a mechanism that allows the immune system to attack cancer cells better than ever before.

The discovery shows promise for lung cancer and the most aggressive type of skin cancer – melanoma. The new mechanism for activating the immune system against cancer cells that allows immune cells to detect and destroy cancer cells better than before has just been published in the prestigious journal Nature.

The study was led by Prof. Nick Haining, of Harvard Medical School, and co-authored by Bar-Ilan’s Prof. Erez Levanon, doctoral student Ilana Buchumansky and an international team. It was titled “Loss of ADAR1 in tumors overcomes resistance to immune checkpoint blockade.” The RNA-editing enzyme ADAR1 in tumor cells profoundly sensitizes tumors to immunotherapy and overcomes resistance to checkpoint
blockade.

The focus of the study is a mechanism that routinely serves the cell by marking human virus-like genes in order to avoid identifying them as viruses. Now, the team has discovered that when inhibiting this mechanism, the immune system can be harnessed to fight cancer cells in a particularly efficient manner – and most effectively in lung cancer and melanoma.

“We found that if the mechanism is blocked, the immune system is much more sensitive. When the mechanism is deactivated, the immune system becomes much more aggressive against the tumor cells,” said Levanon.

In recent years, a new generation of cancer drugs has been developed that blocks proteins that inhibit immune activity against malignant tumors. These drugs have shown remarkable success in several tumor types.

This year’s Nobel Prize in Medicine was awarded to Dr. James Allison and Prof. Tasuku Honjo, who discovered the key genes of this mechanism. Despite this achievement, the current generation of drugs helps only a small number of patients, while most of the drugs fail to cause the immune system to attack the tumor.

It is hoped that the new discovery will allow enhanced activity of the immune system to attack cancer cells. A number of companies have already begun research to screen for drugs that will operate on the basis of this discovery.



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