Antigen and immunotherapy break down barriers of pancreatic cancer

Pancreatic cancer is one of the deadliest forms of the disease, resistant to many treatments. Now, scientists have identified how tumors defend themselves so effectivelyand more importantly, a way to potentially bust through those defenses is uncovered.

Ranking among the leading causes of cancer-related death, the prognosis for pancreatic cancer is disastrous, with less than 10 percent of patients surviving more than five years after diagnosis. One factor that makes pancreatic cancer so difficult is that it forms a cocoon of scar-like tissue called cancer-associated fibroblasts (CAFs), which block chemotherapy and other treatments from getting in.

In the new study, scientists at the University of Texas Southwestern identified another way in which this barrier acts to protect against cancer. Some CAFs have a particularly bad job up their sleeve they present antigens on their surface, which inactivate incoming immune cells to attack the tumor. These antigens convert T cells into regulatory T cells (Tregs), which in turn shut down further immune responses in the region.

To investigate ways to fight back, the researchers performed lineage tracing on antigen-presenting CAFs (APCAFs). This process allowed the team to track how these mediator cells develop over time, as a healthy pancreas becomes cancerous. They found that APCAFs get their start in mesothelial cells, which form a protective lining in organs and other tissues.

With this new understanding, the researchers experimented with a possible way to break down this barrier. In tests in mice with pancreatic cancer, the team implanted the animals with antibodies that targeted mesothelin, a protein component of mesothelial cells. And sure enough, APCAFs were no longer able to interfere with immune cells.

Researchers say the discovery paves the way for new potential treatments for pancreatic cancer in humans by combining anti-mesothelin antibodies with existing immunotherapies. After the antibodies have weakened, immunotherapies can close the door and help take down the tumor.

Of course, far more work needs to be done in animal trials before it can ever be used in human patients. But one day, pancreatic cancer may not be such a death sentence.

The research was published in the journal cancer cell,

Source: UT Southwestern

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