Study links common immune cell to failure of checkpoint inhibitors in lung cancer

Fluorescent-labeled microscopic images — In the microscopic image on the left, large swarms of T cells (dyed light blue) infiltrate a lung cancer patient’s tumor. On the right, high numbers of neutrophils (magenta) have prevented T cells from attacking another patient's cancer. Image courtesy Dr. Xiaodong Zhu

For many lung cancer patients, the best treatment options involve checkpoint inhibitors. These immunotherapy 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 in the journal JCI Insight could help improve those forecasts.

After analyzing tumor samples from 28 patients with non-small cell lung cancer, researchers linked a common immune cell with treatment failure. The culprit: neutrophils, the most abundant type of white blood cell.

The study found 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, a lung cancer immunologist at Fred Hutchinson Cancer Research Center. And it also hints at a way to help patients who have this cellular signature.

In mice with 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. The researchers now want to test this approach in NSCLC patients through a clinical trial.

“As the immunotherapy field has evolved, the main question has become: Can you identify people who will respond to these treatments?” Houghton said. “But here we're really interested in identifying the 80% of people who don't respond and finding new ways to help them.”