Immune checkpoint inhibitors are a type of therapy that uses the immune system to fight cancer. They have been hailed as game changing, garnering a Nobel Prize last year and quickly becoming the standard of care for many tumor types such as melanoma and certain lung and head and neck cancers. But among patients with non-small cell lung cancer who receive checkpoint inhibitor immunotherapy; recent reports suggest that up to 19% may develop a dangerous complication: an inflammation of their lungs; dubbed checkpoint inhibitor pneumonitis.
“They were seeing a lot of patients with this particular type of lung inflammation; but we really didn’t know what was going on in terms of the biology of this disease until now,” says Karthik Suresh, M.D., assistant professor of medicine at the Johns Hopkins University School of Medicine and co-first author of the study’s paper (along with Jarushka Naidoo, M.B.B.Ch., assistant professor of oncology at Johns Hopkins). The paper will be published September 4th, 2019 in the Journal of Clinical Investigation.
Immune checkpoint inhibitor
An immune checkpoint inhibitor (ICI) works by releasing the molecular brakes on components of the human immune system; coaxing the patient’s immune system to attack cancer cells. But turning up the immune system’s activity can also lead to unwanted side effects when the immune system attacks healthy tissues. With NSCLC, one of the relatively common side effects is CIP.
Patients typically develop shortness of breath and a cough; but the illness can progress to be life threatening. Anyone with CIP must stop cancer treatment with immune checkpoint inhibitors; also many are treat with steroids instead. However, some cases don’t respond to steroids; also there is no second-line treatment for CIP that is back by research.
“There are patients who are seeing great results with checkpoint inhibitors when it comes to their cancer; but if they develop this complication, we have to stop their life-changing treatment,” says Franco D’Alessio, M.D., assistant professor of medicine at the Johns Hopkins University School of Medicine and a senior author of the new study. “So figuring out how to treat CIP is of paramount importance to be able to keep patients on track with their cancer treatment.”
Inflammation in their lung
In the new work, Suresh, D’Alessio, Naidoo and their colleagues study tissue collect from the lungs of 12 NSCLC patients with CIP andsix patients being treat with ICIs who hadn’t develop CIP. Patients range in age from 55 to 77; 27.8% were female and 77.8% were Caucasian. Lung cells and surrounding molecules were collect through bronchoalveolar lavage; a procedure in which a small scope is inserted into the airways and fluid is squirt into the lung and then collected.
“Base on the cell types we found; our study suggests several new pathways that be investigate as therapeutic targets,” says Suresh. The findings also help eliminate the use of some treatments for instance; some doctors had using drugs called tumor necrosis factor (TNF) alpha inhibitors to try to treat CIP; but the new study did not observe increase levels of TNF alpha in the bronchoalveolar lavage fluid of CIP patients; perhaps explaining why the drugs have less successful in treating CIP.
The researchers still have questions about why the lung’s immune cells are alter in the first place in CIP patients; also exactly how immune checkpoint inhibitors set off the inflammation. They’re planning follow up studies to answer basic biology questions about the immune cells involve as well as to test drugs that may work against CIP.