Our body houses an arsenal of weapons against infections caused by pathogens such as fungi, bacteria and viruses. T cells are one of those weapons. Indeed, they are among the immune system’s most powerful defense against pathogenic infections and harmful cell mutations like cancer. T cells identify dangers by using a protein on their surface called the T cell receptor that binds to invaders and triggers the immune system to fight them. At the same time, they also carry another protein that acts as a brake on their activity, thus regulating the immune system from attacking our own tissues. This intricate balance between triggers and brakes is nature’s ingenious way of asserting tight control over the immune system.

Until recently, few researchers explored the potential of temporarily braking T cell activity as a form of cancer therapy, which is not surprising considering how preposterous that sounds. Then came along James P. Allison, an immunologist at the MD Cancer Center in Houston, Texas. While other research teams were studying whether the braking mechanism of T cells could be used to treat autoimmune diseases, Allison thought that maybe what is needed to fight cancer was to temporarily halt the braking mechanism so that T cells can be given the chance to eliminate all the cancer cells. When he tested an antibody against the “braking protein” known as CTLA4, he was stunned by the results: mice with cancer were cured by treatment with the antibodies that inhibited the brake and unlocked anti-tumor T-cell activity. A subsequent 2010 clinical study showed this checkpoint inhibition therapy had striking effects in human patients with advanced melanoma. About 20% of people who received the therapy were alive four years after treatment, a result which had never been seen before in this patient group. The trials led to the therapeutic antibody ipilimumab (Yervoy) being approved by the FDA for treating late-stage melanoma.

Meanwhile, a similar story was unfolding in Japan. In 1992, Tasuku Honjo discovered another molecule that influences T cell activity called PD-1. After years of meticulous experiments in his laboratory at Kyoto University, Dr. Honjo was able to show that PD-1 serves as another braking mechanism in the immune system. He then discovered that blocking this brake also triggered attacks on cancer cells, paving the way for another new treatment capable of destroying tumors. Clinical researchers were later able to confirm that his form of checkpoint inhibition led to responses in more patients and also worked against additional forms of cancer. “I was immensely pleased to hear about a patient whose large tumor had been completely cured by PD-1 blockade therapy, and to watch her enjoying a round of golf on a TV program about the breakthrough drug,” Dr. Honjo said of a woman who received the checkpoint inhibitors to combat ovarian cancer.

Today, immunotherapy is the fourth pillar of cancer treatment and is used alongside radiation, chemotherapy and surgery. By orchestrating the immune system in the right way, the two scientists have proved it is possible to control or eliminate cancer in tens of thousands of patients. To honor their discoveries, Allison and Honjo were awarded the 2018 Nobel Prize in Physiology or Medicine “for their discovery of cancer therapy by inhibition of negative immune regulation.”