Some types of cancer drugs target these immunosuppressive proteins.
Tuberculosis affects millions of people worldwide, and is difficult to treat even with extended antibiotic therapy.
“Tuberculosis is a massive global health burden,” said lead author and graduate student Erin McCaffrey from the university.
“Most of the time, the immune system fails to eliminate the bacteria, but it is not known why. We wondered whether the same molecular pathways that protect cancer cells from the immune system also affect the immune response of tuberculosis bacteria.” can,” McCaffrey said.
The researchers used an imaging technique called multiplexed ion beam imaging by time of flight (MIBI-TOF).
Using the technique, they mapped the location of immunosuppressive proteins in granulomas in the lungs and other tissues of 15 people with active TB.
“We saw some of the brightest signals we’ve ever seen compared to cancerous tumors,” said Mike Angelo, assistant professor of pathology at Stanford University Medical Center.
“This indicates the almost universal presence of key immunosuppressive proteins in granulomas,” said Angelo in the study, published in the journal Nature Immunology.
Specifically, the researchers looked at higher levels of two proteins — PD-L1 and IDO1 — that can suppress the immune response to cancer and are often found in tumor tissue. These proteins are targeted by approved cancer drugs.
When McCaffrey and Angelou studied blood samples from more than 1,500 people infected with TB, they found that PD-L1 levels correlated with clinical symptoms.
Patients with latent, or asymptomatic, infections had lower levels of PD-L1 in their blood and were less likely to progress to active infection than those with higher levels of PD-L1.
In contrast, patients with active infections who were considered cured after treatment had a significant reduction in their blood PD-L1 levels compared to those who were not cured.
“We saw a really persistent upregulation of these signals in the blood, which is a sign of a failed immune response,” Angelou said. “They can also be used to predict disease progression from latent to active disease.”