The immune system works vital role In the fight against cancer. Scientists have come to understand this well in recent decades, hence the emergence of Immunotherapy : intensive treatment natural defense to enhance anti-tumor activity. However, within the framework pancreatic cancerthis system is not very efficient. In a press release issued on December 5, researchers from the National Institute of Health and Medical Research (Inserm) found that Receptors present on T lymphocytes Regulatory factors play an important role in suppressing antitumor effects.
Pancreatic ductal adenocarcinoma is the most severe form of the disease. she five-year survival rate After diagnosis no more than 12%. “The tumor is infiltrated by a large number of fibroblasts and supporting cells, forming dense tissue around the tumor. cancer cellwhich Limit drug penetration and immune cells. These fibroblasts secrete immunosuppressive factors that promote cell expansion Can suppress our anti-tumor defenses, especially regulatory T cells : Tregs,” explains Ilaria Cascone, researcher at the Crete Mondo Institute of Biomedical Research, in a press release.
Professor José Cohen and his team of immunology experts explored the role of Tregs. These cells are often very useful When the infection is under control, stop activating our immunity. They also prevent immune system development autoimmune diseases.
In leukemia, scientists demonstrate These lymphocytes can exert harmful effects By suppressing the immune response. “These cells carry a receptor, TNFR2, which binds them Slow down CD8 T lymphocytes : Cells capable of destroying cancer cells. When TNFR2 is blocked with therapeutic antibodies, Tregs are suppressed, T lymphocytes CD8 destroys cancer cells,” explains Dr. Ilaria Cascone.
Immune defenses are ineffective in destroying cancer cells
The research team wanted to know if this This process exists in pancreatic cancer. To achieve this goal, they collected data to confirm these regulatory T cells yes Found in large numbers in pancreatic cancer And they carry TNFR2 receptors.
They then studied mice with cellspancreatic ductal adenocarcinoma. “We observed massive recruitment of Tregs into tumors and strong expression of TNFR2. CD8 T lymphocytes are less common and showed signs of exhaustion, that is, they were unable to mount an effective immune response,” the researchers commented.
A promising initiative opens the way to new treatments
Scientists then tested The role of anti-TNFR2 antibodies to stop this process in mice. The results show Increased CD8 T cellsand those who showed signs of fatigue were reduced, which helped slow the progression of the tumor without destroying it.
To advance this process further, the researchers linked anti-TNFR2 antibodies to molecules that stimulate another receptor, CD40. “Activation of CD40 Enhance CD8 T cell responses. When tested in combination, CD40 agonists enhanced the clinical effects of anti-TNFR2 antibodies: Mice survive longer compared to animals treated with only one of the two molecules,” points out Ilaria Cascone.
“These The results are very encouragingbecause the model developed in mice very faithfully mimics what happens clinically in humans,” explains immunology expert José Cohen. Anti-TNFR2 Antibodies Undergoing Clinical Evaluation Patients with advanced solid tumors. “Promising results have been identified for treating melanoma and pancreatic cancer, which means it could be considered soon. Testing this approach in clinical trials”.
