James Allison and Tasuku Honjo win the Nobel Prize for checkpoint therapy

Historical milestone — this page describes an event dated 2018. It is not current breaking news.

What the prize was for

On October 1, 2018, the Nobel Assembly at Karolinska Institutet awarded the Nobel Prize in Physiology or Medicine jointly to James P. Allison and Tasuku Honjo, "for their discovery of cancer therapy by inhibition of negative immune regulation."

In plainer language: they found the brakes on the immune system, and showed that releasing them lets the body attack cancer.

Why the immune system has brakes at all

T cells are white blood cells that recognize and destroy threats. To do that safely, the immune system needs to tell "self" from "non-self," and it needs a way to stop.

Accelerator proteins push T cells into action. Brake proteins hold them back. The balance keeps the response strong enough to fight infection. It also keeps it from destroying healthy tissue. Those brakes are called immune checkpoints. NCI describes them as a normal part of the immune system.

The problem is that some tumors exploit them. A cancer cell that displays the right partner protein sends an "off" signal to a T cell that had it in its sights.

Allison and CTLA-4

During the 1990s, working at the University of California, Berkeley, James Allison studied a T-cell protein called CTLA-4. He was one of several scientists who saw that it acts as a brake.

Other groups treated that as a target for autoimmune disease. Allison had a different idea. He had already made an antibody that binds CTLA-4 and blocks it, and he asked whether blocking the brake could unleash T cells against cancer.

His group ran the first experiment at the end of 1994 and repeated it over the Christmas break. Mice with cancer were cured by the antibody. Drug company interest was slight at first, but he kept going. In 2010 a clinical study showed striking effects in patients with advanced melanoma. In several of them, signs of remaining cancer disappeared.

Honjo and PD-1

In 1992, a few years earlier, Tasuku Honjo discovered PD-1, a different protein on the surface of T cells. Over years of work at Kyoto University he established that PD-1 is also a brake, operating by a different mechanism.

Animal studies showed that blocking PD-1 was promising, and clinical development followed. In 2012 a key study showed clear effects across several cancer types. Some patients with metastatic cancer had long-term remissions. That condition had previously been considered essentially untreatable.

The first CTLA-4 drug was approved in 2011 and the first PD-1 drugs in 2014.

How checkpoint inhibitors work in practice

NCI explains it simply. Checkpoint proteins such as PD-1 sit on T cells. They bind partner proteins such as PD-L1 on tumor cells. That binding sends an off signal. Some tumors make large amounts of PD-L1 to turn the T cell response down. A checkpoint inhibitor blocks the binding, so the off signal never arrives.

These drugs are now approved across many cancers. NCI's list includes breast, bladder, cervical, colon, head and neck, liver, lung, rectal and stomach cancer. It also includes kidney cancer, Hodgkin lymphoma and melanoma. And it includes any solid tumor that cannot repair errors made when its DNA is copied. Our overview of immunotherapy covers the wider family of treatments.

The side effects follow from the mechanism

Removing a brake on the immune system does exactly what you would expect: sometimes the immune system attacks healthy organs.

NCI lists rash, diarrhea and fatigue as common. Rarer effects involve widespread inflammation. Where it lands decides what it looks like:

• Skin: changes in skin color, rash, itching.
• Lungs: cough and chest pain.
• Colon: belly pain and diarrhea.
• Pancreas: diabetes.
• Liver: hepatitis.
• Pituitary gland: hypophysitis.
• Heart muscle: myocarditis.
• Kidney: nephritis and reduced kidney function.
• Thyroid: an overactive or underactive gland.
• Nerves: muscle weakness, numbness, trouble breathing.

When to get checked

For anyone receiving a checkpoint inhibitor, these are reasons to contact the care team promptly rather than waiting:

• Diarrhea that is new, or more than a few loose stools a day above your usual, or any blood in the stool.
• A new cough, breathlessness or chest pain.
• Yellowing of the skin or eyes, or dark urine.
• A new rash that is spreading, blistering or painful.
• Severe fatigue, dizziness, or feeling faint on standing.
• Palpitations, or chest pressure.
• Unusual thirst and urination, which can signal new diabetes.

These reactions can appear weeks or months into treatment, and sometimes after it ends. NCI notes that doctors and nurses cannot know for sure when or whether they will occur. That is why knowing the signs matters. Our page on immunotherapy sets out what to raise before starting.

What to keep in perspective

• The prize came roughly two decades after the key laboratory work. The gap between a discovery and a treatment people can receive is long.
• Most people who receive checkpoint drugs do not respond. These drugs transformed outcomes for certain groups, not for everyone.
• Serious immune-related side effects are real, occasionally life-threatening, and usually manageable when caught early.
• Approvals are cancer-specific. They often depend on laboratory features of the tumor. A drug approved for one cancer is not automatically available for another.
• This page summarizes a historical event and general medical information. It is not advice about anyone's own treatment.

Our pages on what cancer is and melanoma give the wider background.

Sources

• https://www.nobelprize.org/prizes/medicine/2018/press-release/
• https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors
• https://www.cancer.gov/about-cancer/understanding/what-is-cancer

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

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