A protein commonly found at high levels in lung cancer cells controls a major immunosuppressive pathway that allows lung tumors to evade immune attack, according to a study led by researchers at Weill Cornell Medicine. The discovery could hasten the development of treatments that overcome this tumor defense mechanism and improve outcomes for lung cancer patients.
In the study, which appears Jan. 9 in Nature Communications, the researchers analyzed human lung cancer datasets and performed experiments in preclinical models of lung cancer to show that the transcription factor XBP1s enhances tumor survival by suppressing the anti-cancer activity of neighboring immune cells. They discovered that XBP1s exerts this effect by driving the production of a powerful immunosuppressive molecule, prostaglandin E2.
“We found that XBP1s is part of an important pathway in cancer cells that regulates the local immune environment in lung tumors, and can be disabled to increase anticancer immunity,” said study co-senior author Dr. Vivek Mittal, the Gerald J. Ford-Wayne Isom Professor of Cardiothoracic Surgery and director of the Neuberger Berman Lung Cancer Laboratory at Weill Cornell Medicine.
