Ductal adenocarcinoma of the pancreas is the fourth leading cause of death from cancer in the world. The study of connective tissue, called the stroma that surrounds, nourishes and protects even the tumor is key to the development of effective therapeutic agents.
"Patients with adenocarcinoma often diagnosed too late - says Al Eliade, a researcher at the laboratory of Dr. David Tuvesona. - We can not make a diagnosis in a timely manner due to a lack of tools and reactions to medications. One of the barriers to medication are fibroblasts in the stroma. "
The tumor is characterized by the abundance of non-malignant stromal cells and fibroblasts are one of the most common types of stromal cells. "Unlike other cancers, many of fibroblasts, in pancreatic cancer - says Eliade. - These fibroblasts associated with cancer may help cancer cells multiply, survive and evade the action of the immune system. "
Fibroblasts play a role in protecting the cancer cells, but the complete destruction of the cancer worsened the condition in mice. Eliade and her colleagues investigated the nature of fibroblasts (CAF) associated with cancer. Scientists have used RNA sequencing unicellular for classification of fibroblasts into three subpopulations, defining specific functions and unique characteristics. They identified two previously identified type of CAF, the myofibroblast CAF (myCAF) and inflammatory CAF (iCAF), as well as a new type of CAF, called antigen presenting CAF (apCAF). ApCAF present in both mice and humans with the tumor. The results are published in the journal Cancer Discovery.
Although recently identified apCAF possessed properties fibroblasts, the researchers found that they are different subpopulations of fibroblasts. They expressed MHC class II genes that are normally expressed only by specialized immune cells. Cells with MHC class II molecules on the surface may be foreign antigens or peptides from viruses and bacteria, to assist the T-cells. Detecting the antigen, T-cells activate cytotoxic T cells and other immune components to attack and destroy cancer. But apCAF, present in tumors of the pancreas, there are no other components that activate T cells. Scientists theorize that this could lead to not fully activate T cells, which can not properly destroy the cancer cells.
"We have shown that apCAF have specific possibilities of interaction with T cells so as not to make the other CAF», - says Eliade. Now, the research team plans to study how apCAF interact with T cells and the immune system. "If we can show that apCAF somehow inhibit the activity of T-cells that are able to offer treatments that specifically target this type of CAF, - says Eliade. - We can also combine this method with additional immune therapies for greater efficiency. "