Insights Into Resistance to Immune Checkpoint Inhibitors in Lung Cancer

New research by Yale Cancer Center shows insights into modeling resistance to immune checkpoint inhibitors, a form of cancer immunotherapy. The study was presented today at the American Association of Cancer Research (AACR) virtual annual meeting.

"Acquired resistance to immune checkpoint inhibitors is a growing clinical challenge. About 50% of lung cancer patients who initially respond to immune checkpoint inhibitors eventually develop acquired resistance to these therapies," said Camila Robles-Oteiza, lead author of the study from Yale Cancer Center. "We studied this clinical challenge by examining the mechanisms of resistance to help improve treatment."

Yale researchers used a novel mouse model of KRAS-driven lung cancer to investigate what drives acquired resistance to immune checkpoint inhibitors. They found lung tumors with acquired resistance to these therapies have reduced expression of MHC-II molecules, as well as increased tumor hypoxia or where tumor cells have been deprived of oxygen. By combining immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 with an anti-hypoxia agent, researchers showed they could slow the acquired resistance.

"Informing strategies to overcome acquired resistance can help to address a critical, unmet need in cancer therapy," said Robles-Oteiza.

Other authors of the study from Yale are Katerina Politi, PhD, senior author and co-authors Susan M. Kaech, PhD and Katherine Hastings, PhD.

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