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James Allison and Tasuku Honjo, cancer immunotherapy trailblazers, take home 2018 Nobel Prize in medicine

James P. Allison and Tasuku Honjo won the 2018 Nobel Prize in Physiology or Medicine for their groundbreaking work in cancer immunotherapy.

Cancerous tumors are notoriously skilled at dodging our immune systems. That’s because our immune systems typically fight off foreign invaders, such as bacteria and viruses, and mostly ignore the cells created within our bodies — which include cancer cells.

Cancer immunotherapy is an emerging branch of medicine that calls on our immune systems to act as intermediaries in the battle against a tumor. This practice contrasts with radiation therapy and standard chemotherapy, which directly attack cancerous tumors.

Both Allison and Honjo discovered how to lift the molecular “brakes” that keep our immune cells from attacking ourselves — specifically the cancer cells that spawn inside of us.

Who are the winners

James P. Allison, 70, was born in Alice, Texas. He works as an immunologist at the M.D. Anderson Cancer Center in Houston. Immunologist Tasuku Honjo, 76, conducts his research at Kyoto University in Japan. He was born in Kyoto.

What they did

Allison and Honjo developed ways to unleash our T-cells — one of the major bodyguards of our immune systems. Their procedures relied on antibodies — proteins made to bind and interfere with other proteins.

In the early 1990s, Allison had been studying a protein called CTLA-4, which sits in the outer layer — the membrane — of an active T-cell and behaves like an off-switch.

Allison and his lab found when they injected antibodies that interfere with CTLA-4, the T-cells began multiplying like crazy. Rapidly producing a broad diversity of T-cells increases the likelihood of making a T-cell that would recognize and would kill an evasive tumor. In other words, this cancer therapy relies somewhat on serendipity.

Honjo’s therapy takes a similar but more direct approach. In 1992, his lab found another off-switch for T-cells embedded in their membranes: a protein called PD-1.

Normally, PD-1 proteins work like sunglasses. They protect our T-cells from becoming overexposed to foreign invaders and, as consequence, too revved up. In this situation, the T-cells recognize that something is wrong in the body, but it isn’t being fixed. So, PD-1 shuts off the T-cells activity to prevent them from becoming exhausted.

This scenario can also occur when a person has had a cancer for a long time. Some types of cancers can adapt to intentionally stimulate PD-1 on T-cells, causing the immune system bodyguards to take a hike.

Honojo’s lab discovered when they injected antibodies against PD-1 that cancer cells could no longer dupe the T-cells. As a result, the T-cells could kill the cancer cells.

Why it matters

Cancer immunotherapies are less harmful to human tissue than traditional treatments like radiation and classic chemotherapy, which reduces the likelihood of unmanageable side effects.

Today, immunotherapies based on Allison and Honjo’s research are approved for treating melanoma, bladder cancer, colorectal cancer, liver cancer and lung cancer — though this represents a small slice of tumor-related diseases experienced by patients.

Though cancer rates continue to decline in the U.S., this class of diseases remains a persistent medical burden. In 2018, more than 1.7 million in the U.S. will develop a tumor for the first time, and nearly 600,000 people will be killed by cancer. Worldwide, cancer is the second leading cause of mortality–with 70 percent of these deaths occurring in low- and middle-income countries.

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