Pancreatic cancer is one of the deadliest cancers in Switzerland, with around 1,400 deaths per year. Despite medical advances, the prognosis remains poor: about 87 percent of patients die within five years of diagnosis. One of the main reasons for this is the high resistance of this tumor type to existing therapies—largely due to its unique, well-shielded structure.
A Wall of Fibrous Tissue Protects the Tumor
A key characteristic of pancreatic cancer is fibrosis, an abnormal overgrowth of dense connective tissue around the tumor. This hardening acts like an internal scar. It impairs blood flow and prevents immune cells and medications from effectively reaching and attacking the cancer cells. Fibrosis is mainly caused by cancer-associated fibroblasts (CAFs). Fibroblasts are connective tissue cells that produce important components like proteins (e.g., collagen), providing stability and structure to tissue. In the tumor environment, however, CAFs not only promote tumor growth but also therapy resistance and metastasis.
Despite their key role in the tumor environment, there are currently very few targeted therapies against CAFs. Existing treatments mostly focus on the tumor cells themselves. This is where the research project led by Professor Christian Stockmann at the Institute of Anatomy, University of Zurich, comes in. The team has developed an immunotherapeutic vaccine that specifically targets a protein called ADAM12, which is mainly found in activated fibroblasts—precisely the cells responsible for forming the fibrotic protective layer. The researchers aimed to activate the immune system through the vaccine to recognize, attack, and destroy the CAFs without damaging healthy tissue.
Targeted Attack on the Tumor Environment
In several mouse models, the vaccine showed a clear therapeutic effect: tumors grew more slowly and remained significantly smaller. The number of CAFs causing fibrosis decreased, along with the amount of dense connective tissue around the tumor. Additionally, the number of certain immune cell types in the tumor environment changed: inflammatory immune cells decreased, while specific subtypes of T cells increased. Detailed analyses of the tumor tissue also showed increased activity of these T cell subtypes against tumor cells expressing ADAM12 on their surface. This suggests that the vaccine triggered a targeted immune response against the tumor.
A frequently discussed risk when destroying fibroblasts is that healthy tissue—such as important support cells in blood vessels—might be unintentionally affected. This could worsen oxygen supply and even promote tumor growth. However, the opposite was observed: the vaccine improved blood vessel structure and reduced oxygen deficiency in the tumor. As a result, the aggressiveness of tumor cells decreased, and liver metastases occurred less frequently.