Immune checkpoints are a natural part of the human body’s immune system; they prevent the immune system from going into overdrive, which can result in damaging inflammation. But the immune system is a powerful offense against cancer, so scientists have come up with various drugs meant to stimulate the immune system in cancer patients.
Checkpoint inhibitors are a specific type of immunotherapy that prevent the immune system from “checking” itself. However, in a study published today in eLife, University of Southampton researchers have identified how new checkpoint inhibitor treatments can activate tuberculosis in some patients.
University of Southampton researchers described one of the earliest cases of immunotherapy-associated tuberculosis in December 2018 in the American Journal of Respiratory and Critical Care Medicine, and reports of similar cases have progressively accumulated. However, the true incidence is unknown, as progression of cancer and the development of tuberculosis can be similar.
To understand the mechanisms underlying this emerging phenomenon, researchers used a 3D cell culture model to measure the effect of checkpoint inhibitors on the immune system’s ability to control the bacteria that cause tuberculosis. The team’s findings demonstrate that the addition of an immune checkpoint inhibitor called anti-PD1 led to an excessive immune response, which actually increased growth of the bacteria.
“This is an important emerging clinical phenomenon, and by understanding the process that leads to increased tuberculosis growth, we can identify existing treatments that could be used to reduce severity of infection and permit continuation of the cancer treatment,” says first author Liku Tereza. “This may improve outcomes when this surprising side effect of emerging cancer immunotherapies occurs.”
The researchers are currently aiming to establish a national register to capture the true incidence of this phenomenon, and they are also developing the laboratory system to predict what other new cancer therapies may have a similar effect.
Image: Lung damage caused by TB infection. Image courtesy of University of Southampton.