Ratio of Neutrophils to T Cells in Tumor Environment Can Help Predict Which Patients Will Respond to Checkpoint Inhibitor Immunotherapy in Lung Cancer; Study Suggests That Neutrophil-Blocking Drugs May Boost Effectiveness of Checkpoint Inhibitors

For many lung cancer patients, the best treatment options involve checkpoint inhibitors. These drugs unleash a patient's immune system against their disease and can yield dramatic results, even in advanced cancers. But checkpoint inhibitors come with a huge caveat: They only help a small subset of patients. Doctors struggle to predict who these patients are and -- just as important -- who they aren't. Results from a new study published online on December 18, 2019 in JCI Insight could help improve those forecasts. The open-access article is titled “Neutrophil Content Predicts Lymphocyte Depletion and Anti-PD1 Treatment Failure In NSCLC.” After analyzing tumor samples from 28 patients with non-small cell lung cancer(NSCLC), researchers linked a common immune cell with treatment failure. The culprit: neutrophils, the most abundant type of white blood cell. The paper shows that the balance between neutrophils and another type of immune cell -- disease-fighting T cells -- could accurately predict which patients would respond or not. If more neutrophils than T cells were crowded into a tumor, the drugs did not curb the patients' cancers. But if the balance was reversed, checkpoint inhibitors revved up patients' immune systems against their disease. "The study is the first to implicate neutrophils in the failure of checkpoint inhibitors," said senior author Dr. McGarry Houghton, MD, a lung cancer immunologist at Fred Hutchinson Cancer Research Center in Seattle, Eashington. "Our findings also hint at a way to help patients who have this cellular signature." In a mouse model of NSCLC, the researchers administered a drug that decreased the number of neutrophils in and around tumors. That, in turn, boosted the efficacy of checkpoint inhibitors -- T cells now had a clear path to attack diseased cells in the mice.
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