Pancreatic cancer is one of the most deadly forms of the disease, resistant to many treatments. Scientists have now identified how tumors defend themselves so effectively – and more importantly, are discovering a way to potentially overcome those defenses.

Among the leading causes of cancer-related deaths, the prognosis for pancreatic cancer is devastating, with less than 10 percent patients who survived more than five years after diagnosis. One of the factors that makes pancreatic cancer so difficult is that it builds a cocoon out of scar-like tissue called cancer-related fibroblasts (CAFs), which prevents chemotherapy and other treatments from entering.

In a new study, researchers at Southwestern University in Texas identified another way in which this barrier works to protect against cancer. Some CAFs have a particularly nasty trick up their sleeves – they present antigens on their surface that disarm the immune cells that come to attack the tumor. These antigens convert T cells into regulatory T cells (Tregs), which in turn inhibit further immune responses in the region.

To investigate ways to fight back, the researchers tracked the line of antigen-presenting CAFs (apCAFs). This process allowed the team to track how these intervening cells develop over time as the healthy pancreas becomes cancerous. They found that apCAFs begin to form in mesothelial cells, which form a protective sheath in organs and other tissues.

Armed with this new understanding, the researchers experimented with a potential way to break through this barrier. In tests on mice with pancreatic cancer, the team dosed the animals with antibodies targeting mesothelin, a protein component of mesothelial cells. And certainly apCAFs could no longer interfere with immune cells.

Researchers say the discovery paves the way for new possible treatments for pancreatic cancer in humans by pairing anti-mesothelin antibodies with existing immunotherapies. Once the antibodies weaken the defenses, immunotherapies can break down the door and help remove the tumor.

Of course, much more work needs to be done on animal testing before they can be used in humans. But one day pancreatic cancer may not be such a death sentence.

The study was published in the journal Cancer cell.

Source: UT Southwest

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