Proteins associated with cancer growth can promote fatal lung disease

Idiopathic pulmonary fibrosis (IPF) is a disease with unknown causes, which causes lung scarring and stiffness. As time goes by, scars will worsen and stiffness will make breathing more difficult. Ultimately, the lungs may not be able to absorb enough oxygen to provide the body with the oxygen it needs, which can lead to respiratory failure, heart failure, and other health problems. According to statistics, although different patients have a different onset, most patients have a survival period of no more than five years.

Unfortunately, there are currently no known treatments for IPF and no treatment options. Existing FDA-approved drugs only slow or treat some people's fibrosis and other symptoms.

A study published in the JCI Insight journal revealed that proteins associated with cancer growth seem to drive deadly IPF. This study provided a promising strategy for the development of treatment for IPF.

Researchers focused on cells called fibroblasts, a group of highly active cells. One of the most obvious functions is to synthesize proteins. Collagen synthesized by fibroblasts is an important component of the extracellular matrix (ECM). Extracellular matrix is an intricate network of macromolecules that provides a suitable site for cell survival and activity and affects cell shape, metabolism, function, migration, proliferation, and differentiation through signal transduction systems.

In idiopathic pulmonary fibrosis, defective fibroblasts invade normal lung tissue and produce excessive fibrous (scar) tissue deposits that progressively impair lung function.

When investigating lung tissue samples from patients with idiopathic pulmonary fibrosis, the researchers found that invasive fibroblasts secrete high levels of PD-L1 (programmed death ligand 1), a protein expressed on normal cells. When the PD-L1 expressed by the cells binds to PD-1 expressed on immune cells, the immune cells can be inhibited from attacking these cells. Invasive fibroblasts successfully escape the destruction of the body's immune system by "disguising" for normal cells.

Subsequent research by the team demonstrated that the introduction of normal fibroblasts did not result in pulmonary fibrosis and that the suppression of PD-L1 by genetic and antibody techniques reduced the severity of the disease.

They combined these results to identify PD-L1 as a driver of fibroblast invasion in idiopathic pulmonary fibrosis and support PD-L1 as a potential therapeutic target for this condition.

The team is preparing to design a clinical trial using PD-L1 inhibitors against the disease. The trial will assess the safety of this drug to patients. If found to be safe, the drug can be tested in subsequent trials to assess its effectiveness and further test its safety.

Some cancer cells block the attack of the immune system by secreting PD-L1, a process called immune evasion. Considering that several PD-L1 inhibitors are currently approved by the FDA for the treatment of cancer. The investigators recommend using one of these FDA-approved drugs in clinical trials of idiopathic pulmonary fibrosis.