The fight against cancer is an arms race, and one of the most effective weapons in clinicians' arsenals is immunotherapy . Immune checkpoint therapy has become the standard for treating several types of cancer. However, the Nobel Prize-winning strategy is ineffective for most pancreatic ductal adenocarcinoma (PDAC) patients.
Immune checkpoint therapy is only an option in rare cases of PDAC. It's only effective for patients with a specific subtype of PDAC-;that's less than 5% of all cases." Douglas Fearon, Professor, Cold Spring Harbor Laboratory (CSHL) Until recently, it was thought that PDAC didn't trigger any kind of immune response.
In 2023, Fearon and his team confirmed the opposite. Immune cells do go on the attack. But they struggle to infiltrate the deadly tumors, which allows PDAC to avoid destruction.
Now, Fearon and former CSHL postdoc Jiayun Li have discovered that a common chemotherapy supplement called folinic acid weakens the cancer's defenses in mice. They found that folinic acid elevates levels of two anti-cancer immune molecules within PDAC: natural killer T (NKT) cells and type-I interferons. In mice, this leads to a more effective immune response, slower tumor growth, and longer survival.
"We discovered that NKT cells enabled type-I interferon to be produced and, as a consequence, adaptive immune killing and expansion of T cells would occur," says Fearon. "T cells respond to tumors, but they typically cannot get in there unless type-I interferon is produced.