Antigens and immunotherapy break through pancreatic cancer's barriers
Pancreatic cancer is one of the most deadly forms of the disease, resistant to many treatments. Now, scientists have identified how the tumors protect themselves so effectively – and more importantly, uncovered a way to potentially bust through those defenses.
Ranking among the leading causes of cancer-related deaths, the prognosis for pancreatic cancer is devastating, with less than 10 percent of patients surviving beyond five years after diagnosis. One factor that makes pancreatic cancer so tough is that it builds a cocoon of scar-like tissue called cancer-associated fibroblasts (CAFs), which prevents chemotherapy and other treatments getting in.
In the new study, scientists from the University of Texas Southwestern identified another way that this barrier works to protect the cancer. Some of the CAFs have a particularly nasty trick up their sleeves – they present antigens on their surface, which disarm immune cells that come to attack the tumor. These antigens convert T cells into regulatory T cells (Tregs), which in turn shut down further immune responses in the area.
To investigate ways to fight back, the researchers conducted lineage tracing on the antigen-presenting CAFs (apCAFs). This process allowed the team to track how these meddlesome 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.
Armed with this new understanding, the researchers experimented with a potential way to break through this barrier. In tests in mice with pancreatic cancer, the team dosed the animals with antibodies that targeted mesothelin, a protein component of mesothelial cells. And sure enough, the apCAFs were no longer able to interfere with immune cells.
The researchers say that this discovery paves the way for new possible treatments for pancreatic cancer in humans, by pairing anti-mesothelin antibodies with existing immunotherapies. After the antibodies weaken the defenses, the immunotherapies can bust the door down and help take down the tumor.
Of course, far more work needs to be done in animal tests before that could ever be used in human patients. But one day, pancreatic cancer might not be such a death sentence.
The research was published in the journal Cancer Cell.
Source: UT Southwestern