Trying everything they could in mice to tweak the immune system, Krummel and Allison soon found that a protein receptor called CTLA-4 seemed to be holding T cells back, like a brake in a auto.
Honjo, who has been a professor at Kyoto University since 1984, separately discovered a second protein on immune cells and revealed that it too operated as a brake, but with a different mechanism.
Many of Allison's patients are alive and cancer free because of his approach.
Allison focused on a protein on the surface of T cells called CTLA-4, discovering that it inhibits the immune cells.
The two men won the prize for their landmark discovery of "cancer therapy by inhibition of negative immune regulation". Research by Allison at the University of Texas in the USA and Honjo at Japan's Kyoto University explored how the body's immune system can be harnessed to attack cancer cells by releasing the brakes on immune cells. "I didn't set out to study cancer, but to understand the biology of T cells, these incredible cells [that] travel our bodies and work to protect us". The victor of the Nobel Peace Prize will be named Friday. Other scientists worked on using CTLA-4 as a way to treat autoimmune disorders. The result is dramatically improved outcomes for some cancer patients and an explosion of research into ways to build on progress made to date.
Their work centers on harnessing the immune system to arrest the development of cancer.
Antibodies against PD-1 have been approved by the US Food and Drug Administration as an investigational new drug for the treatment of cancer.
"I never dreamed my research would take the direction it has", Allison adds.
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Dr Allison, 70, said he was "honoured and humbled to receive this prestigious recognition".
He was recruited back to MD Anderson in November 2012 to lead the Immunology Department and to establish an immunotherapy research platform for MD Anderson's Moon Shots Program.
In 2016, after being treated with a drug inspired by Prof Honjo's research, he announced that he no longer needed treatment.
"We need these drugs to work for more people", Allison said.
He said Allison's work a decade ago "really opened up immunotherapy" as a fifth pillar of cancer treatments, after surgery, radiation, chemotherapy and precision therapy. Allison's success with CTLA-4 in cancer persuaded Honjo to consider his molecule in cancer as well-and he found PD-1 therapy was even safer and more effective against a number of cancers, including lung cancer, which kills about 150,000 Americans a year.
For the first time since 1949, the Swedish Academy has postponed the announcement of the 2018 Nobel Literature Prize until next year, amid a #MeToo scandal and bitter internal dispute that has prevented it from functioning properly.
No literature prize is being given this year.