Discoveries about ways to harness the immune system to attack cancer have won the 2018 Nobel Prize for Physiology or Medicine. James Allison of the University of Texas MD Anderson Cancer Center in Houston and Tasuku Honjo of Kyoto University in Japan each discovered ways to remove the immune system’s “brakes” that prevent it from attacking tumor cells.

Such cancer immunotherapies have revolutionized treatment of certain types of cancer, causing previously untreatable tumors in some patients to shrink to almost nothing.

"James Allison studied a known protein that functions as a brake on the immune system. He realized the potential of releasing the brake and thereby unleashing our immune cells to attack tumors," the Nobel Assembly at the Karolinska Institute said in an announcement this morning . "He then developed this concept into a brand new approach for treating patients."

"In parallel, Tasuku Honjo discovered a protein on immune cells and, after careful exploration of its function, eventually revealed that it also operates as a brake, but with a different mechanism of action. Therapies based on his discovery proved to be strikingly effective in the fight against cancer."

“The time is right. Patients have been treated for several years now and we can now see the long-term outcome. It’s very convincing.”

“The time is right,” Klas Kärre, an immunologist at the Karolinska Institute in Stockholm and a member of the Nobel Committee told a press conference. “The first approved drug based on this treatment came in 2011. Patients have been treated for several years now and we can now see the long-term outcome. It’s very convincing.”

Allison’s discoveries built on the work of French immunologists from the 1980s who were studying T cells, components of the immune system that attack cells that the body recognizes as foreign. They identified a key receptor on the surface of T cells that they called cytotoxic T-lymphocyte antigen 4, or CTLA-4. Allison and others found that the receptor puts the brakes on T cells, preventing them from launching full-out immune attacks. Other groups hoped to use the receptor to help in treating autoimmune disease—in which the immune system’s brakes aren’t strong enough. But Allison had a different idea. Cancer develops when the body’s immune system fails to attack tumor cells, even though they are growing out of control; Allison wondered whether blocking the blocker—the CTLA-4 molecule—would set the immune system free to destroy cancer.

This was a new concept—to target the body’s system of immunosuppression as a tool to help defeat tumors. In 1996, Allison published a paper in Science showing that antibodies against CTLA-4 erased tumors in mice.

Pharmaceutical companies initially shied away from cancer immunotherapy, wary of possible side effects and also of an approach so different from the standard treatments of surgery, radiation or chemotherapy. So the job of getting anti–CTLA-4 into people fell to a small biotechnology company, Medarex, in Princeton, New Jersey. It acquired rights to the antibody in 1999 and were the first to use it as a drug.

Honjo, meanwhile, in the early 1990s discovered a molecule expressed in dying T cells, which he called programmed death 1, or PD-1. He recognized PD-1 as another brake on T cells, and he and others performed key experiments showing that the molecule could also be a target in cancer therapies. The first clinical trials using PD-1 were even more dramatic than those with CTLA-4. Several patients with metastatic cancer—tumors that had spread to multiple sites in the body—were apparently cured. And side effects seemed milder than those observed with CTLA-4 therapies.

Science named cancer immunotherapy the Breakthrough of the Year in 2013 .  An overview of the field is in this special issue from March 2018 .

This story will be updated throughout the day.