TIGIT Checkpoint Inhibitor Discovered to Promote Tissue Healing Beyond Cancer Treatment
Key Insights
University of Zurich researchers have identified a new function of the immune checkpoint inhibitor TIGIT (search), showing it promotes tissue healing through specific growth factor production in immune cells.
Mice lacking TIGIT (search) developed significantly more tissue damage in blood vessel walls and liver during viral infections, confirming the protein's protective role against tissue damage.
The discovery reveals TIGIT (search)'s dual role in balancing immune defense with tissue protection, potentially opening new therapeutic avenues for chronic wounds (search) and liver fibrosis (search) treatment.
Researchers at the University of Zurich have uncovered a previously unknown function of TIGIT (search), a well-established immune checkpoint inhibitor used in cancer (search) treatment, demonstrating its critical role in promoting tissue healing and repair. The discovery, published in Nature Immunology, could revolutionize treatment approaches for chronic wounds (search) and fibrotic diseases.
Novel Mechanism of Tissue Protection
The research team, led by Professor Nicole Joller from UZH's Department of Quantitative Biomedicine, identified the specific signaling pathway through which TIGIT (search) promotes tissue repair. "We suspected that TIGIT also has something to do with tissue repair. However, the underlying mechanisms were completely unknown until now," Joller explained.
Using mice infected with the rodent virus LCMV, researchers compared tissue damage between animals lacking the TIGIT (search) gene and control groups. Mice without TIGIT developed significantly more tissue damage, particularly in blood vessel walls and the liver, confirming the checkpoint inhibitor's protective role.
Growth Factor Production Discovery
The investigation revealed that only immune cells equipped with TIGIT (search) produced a specific growth factor in response to viral infection. This growth factor activates multiple repair mechanisms and serves as a central component in tissue regeneration. Further experiments demonstrated how TIGIT upregulates the gene responsible for this critical growth factor production.
"Our findings show that TIGIT (search) promotes the production of a growth factor in immune cells—one that is critical for repairing tissue after viral infections," Joller noted. The team successfully identified and described this previously unknown function of checkpoint inhibitors.
Clinical Implications and Therapeutic Potential
The research sheds new light on the delicate balance between immune defense and tissue protection. The findings could enhance understanding of tissue-damaging effects from viral infections, including influenza (search) and COVID-19 (search), which are known to cause severe damage to blood vessel walls, liver, and lungs.
Joller sees considerable promise for innovative treatments targeting conditions affecting tissues, such as chronic wounds (search) and liver fibrosis (search)—a disease characterized by scar tissue buildup. "We could potentially activate the TIGIT (search) checkpoint to accelerate the regenerative process," she suggests.
Broader Impact on Immunotherapy
This discovery adds a new dimension to the understanding of immune checkpoint inhibitors (search), which are primarily known for their role in cancer (search) therapy where they are disabled to allow the immune system to fight tumor cells more effectively. The identification of TIGIT (search)'s tissue-healing properties reveals the complex dual nature of these regulatory mechanisms.
"Our results shed new light on the balance between immune defense and tissue protection," Joller emphasized. The research demonstrates that checkpoint inhibitors serve as natural protective mechanisms that curb overzealous immune responses while simultaneously promoting tissue repair and regeneration.