Italian Researchers Make Progress in Targeting Pancreatic Cancer
A breakthrough discovery made by Italian researchers offers new hope in the battle against pancreatic cancer, one of the most aggressive forms of the disease. The study, published in the journal Nature, identifies a mechanism that fuels the growth of pancreatic tumors, providing a potential therapeutic target to slow down the progression of the disease.
Led by the San Raffaele Institute of Milan in collaboration with the Telethon Institute of Gene Therapy and the Vita e Salute University, the research also involved the Universities of Turin and Verona, the French Institute for Health and Medical Research (Inserm), the Biopolis research center in Singapore, and the University of Shanghai.
While the researchers acknowledge that they are still far from reaching a therapy that can be applied to patients, they believe they have taken a significant step forward in understanding the biological processes behind pancreatic cancer. Supported by the Airc Foundation for cancer research, European Research Council, and Ministry of Health, they emphasize that further research is needed to fully explore the potential and best approaches to target this newfound therapeutic pathway.
Pancreatic ductal adenocarcinoma, the specific form of pancreatic cancer targeted in this study, benefits from a special alliance between a type of immune cells called IL-1beta+ macrophages and aggressive tumor cells associated with inflammation. This alliance creates a self-sustaining vicious circle, where macrophages make tumor cells more aggressive, and tumor cells, in turn, reprogram macrophages to promote inflammation and disease progression.
Macrophages, normally part of the body’s innate immune system that rapidly responds to protect tissues, undergo reprogramming in the case of tumors and contribute to the disease. Termed “tumor-associated macrophages” or ‘Tam,’ they are crucial targets for immunotherapy. However, targeting them in pancreatic cancer presents significant challenges. The newfound alliance between macrophages and tumor cells could potentially change this situation.
Pancreatic cancer is known for its compromised immune system, which limits the effectiveness of advanced immunotherapies. Additionally, the disease has a strong inflammatory component, with tissue damage and resulting inflammatory responses serving as known risk factors for the development of pancreatic cancer.
Unraveling the intricacies of these immune cells required advanced technologies and extensive collaboration between different disciplines, from genetics to bioinformatics, as well as between researchers and doctors at the IRCCS San Raffaele hospital. The researchers obtained the molecular profile of thousands of macrophages collected from patients with pancreatic cancer, allowing them to identify a subgroup of macrophages specialized in making tumor cells more aggressive. These macrophages nest close to the diseased cells and induce inflammation, while the transformed tumor cells, in turn, strengthen the macrophages.
The next step in the research is to break this alliance, particularly by moving macrophages away from tumor cells. Although the results have only been observed in laboratory studies so far, they have been encouraging according to Nicoletta Caronni and Francesco Vittoria, two of the main authors of the article.
Pancreatic cancer is notorious for its low survival rates, often diagnosed at advanced stages when treatment options are limited. This new discovery brings hope for future therapies and offers a potential breakthrough in the fight against this deadly disease.