Unleashing the Immune System on Cancer

This year has its work cut out if it wants to compete with the achievements of 2018. Immunotherapy was formally recognized with a Nobel Prize in Physiology or Medicine awarded to two researchers for their work with immune checkpoint inhibition. The research pioneered the way towards harnessing a patient’s immune system to attack and destroy the once hidden tumor cells.

Immune checkpoints such as PD-1 serve the immune system as a sort of stop signal that helps to turn-off its action. Unsolicited immune responses can be detrimental to the patient if left unchecked. However, when it comes to cancer, often the tumor cells are equipped with the off-signal as immune cells venture nearby. With the development of drugs to inhibit these checkpoints both with immune cell surface proteins as well as the tumor cells, tumors began to shrink!

“PD-1 is a checkpoint protein on immune cells called T cells. It normally acts as a type of off switch that helps keep the T cells from attacking other cells in the body,” the American Cancer Society explains. “It does this when it attaches to PD-L1, a protein on some normal (and cancer) cells. When PD-1 binds to PD-L1, it tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them evade immune attack.”

Unfortunately, the immunotherapy can still become stunted when faced with acquired mutations that impair antigen presentation. Researchers have set out to unleash the power of the immune system a step further by manipulation of a mechanism that better activates the immune system against cancer by way of tumor cell detection and destruction.

A team of international researchers including Professor Nick Haining, of Harvard Medical School and co-author Professor Erex Levanonm doctoral student Ilana Buchumansky, of the Mina and Everard Goodman Faculty of the Life Sciences at Bar-Ilan University publish their findings in Nature describing a critical aspect of immune power against cancer.

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

The mechanism that the researchers focus on is responsible for marking the cells of human virus-like genes to avoid identifying them as a virus. When the researchers inhibit the mechanism, the immune system acts in a more aggressive manner killing the cancerous cells.

The research team shows that loss of function of “the RNA-editing enzyme ADAR1 in tumor cells profoundly sensitizes tumors to immunotherapy and overcomes resistance to checkpoint blockade.” When the genetic code is removed, the result is of tumor growth inhibition and tumor inflammation.

The research team hopes that this discovery will aid in future therapies to rid patients of their cancer. Physicians might one day in the future be able to make use of this discovery to improve the prognosis of patient health, especially when other cancer treatments such as chemotherapy, radiation, and immune checkpoint blockade is no longer a viable option.

Sources: Forbes, Nature, YouTube