Exploring Cancer Drugs as a Potential Treatment for Pulmonary Fibrosis

Researchers from Tulane University have uncovered a promising new approach to treating idiopathic pulmonary fibrosis (IPF), a severe and currently incurable lung disease affecting over 3 million people worldwide. IPF is characterized by progressive scarring in the lungs, leading to difficulty in breathing and a high mortality rate, with about half of the patients dying within three years of diagnosis. Present treatments primarily aim to slow disease progression but cannot reverse existing damage.

In a groundbreaking study published in the Journal of Clinical Investigation, scientists investigated the role of immune system modulation using an FDA-approved cancer medication. Their findings suggest that this drug may enable the immune system to clear out damaged, senescent cells responsible for lung scarring, potentially restoring lung function.

The disease involves fibroblasts—cells responsible for tissue repair—becoming dysfunctional in IPF. Some fibroblasts and adjacent epithelial cells enter a senescent state, ceasing to divide or die properly, which leads to their accumulation and the formation of stiff, scarred lung tissue. The research identified that these senescent cells tend to gather when the immune system's natural ability to eliminate them is impaired, with the protein CTLA4 acting as a brake on immune activity.

The team focused on ipilimumab, an immunotherapy drug already used in cancer treatment, to block CTLA4 in mouse models. This intervention activated T cells, immune cells that can destroy senescent fibroblasts, enhancing lung tissue regeneration and reducing scarring in the mice. Senior author Dr. Victor Thannickal explained that CTLA4 normally limits inflammation to prevent immune overactivity, but in IPF, overexpression hampers the removal of harmful cells. Blocking this protein effectively 'releases the brakes' on the immune response.

Analysis of human and mouse lung tissues revealed elevated levels of CTLA4 in areas of significant scarring. Mice treated with ipilimumab showed faster and more effective lung repair than untreated counterparts, indicating a potential therapeutic pathway.

Lead researcher Santu Yadav highlighted that instead of killing senescent cells directly, this approach reactivates the immune system to perform this task naturally. However, further studies are needed to determine safe dosing strategies to prevent excessive immune activation, which could cause unintended inflammation.

As IPF primarily affects older adults, these findings also raise hope for broader applications in other aging-related diseases where senescent cell accumulation is a factor, such as Alzheimer's and certain cardiovascular conditions. Thannickal emphasized that successfully activating T cells to clear senescent cells without collateral damage could revolutionize the treatment of various age-linked diseases and potentially slow or reverse aging processes.

This research opens new avenues for immune-based therapies in pulmonary fibrosis and possibly extends to other age-associated disorders, marking a significant step toward innovative treatments.

Source: https://medicalxpress.com/news/2025-04-pulmonary-fibrosis-cancer-drug.html