How pancreatic cancer’s most aggressive cells evade our defenses

Estimated reading time: 5 minutes

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Fountain: CNIO

Rights: Creative Commons.

He pancreas cancer It is usually detected in late stages and very resistant to chemotherapy. Part of its aggressiveness is due to the fact that some of its cells, the so-called cancer stem cellshave the ability to restart the tumor and get out from under the body’s defense system.

After decades of trying to understand how they achieve this, Spanish research teams are now revealing their strategy: pancreatic cancer stem cells evade protective cells by “masking” themselves with a protein that normally serves to protect themselves.

This discovery may facilitate the effectiveness of immunotherapy-based treatments in pancreatic cancer. Susana Garcia-Silvaresearcher at the National Center for Cancer Research (CNIO): “The challenge now is to block the protein we discovered and see whether it is an effective therapy against pancreatic cancer alone or as a combination treatment.”

“Immunotherapy, which redirects the body’s natural defenses against tumors, is today the most effective treatment for advanced cancer. But they don’t work on this tumor,” explains Garcia-Silva, co-author of the study. This is a study that used animal models and patient samples.

“For them to be effective in the pancreas, we must understand tumor immunorescue strategies, especially cancer stem cells, since they are what support its growth,” he adds. The results were published in the journal intestine.

Relevant protein for cancer

The protein that pancreatic cancer stem cells use to protect themselves from host cells surprised Garcia-Silva. Called PGLYRP1 and it belongs to a family of proteins present in organisms as diverse as insects and mammals, which generally implies that it has been conserved throughout evolution because it plays an important role.

A new study shows that it is unexpectedly found in cancer. The normal function of PGLYRP1 is to be part of the immune system as a response agent to bacterial attacks; However, pancreatic cancer stem cells use it for a different task: to disguise themselves as cells of the defense system and camouflage themselves among the cells that should destroy them.

“It was already known that tumor cells use defense proteins to camouflage themselves and escape, but the use of a protein with antibacterial properties as an immunoresistance strategy in cancer had not been described,” says the researcher.

New treatments in development

We now know that the role of PGLYRP1 in pancreatic cancer is “very relevant,” Garcia-Silva says. “If a cancer cell is alone and has to fight off the immune system, it needs this protein to evade it, grow and generate a tumor. PGLYRP1 is important in the early moments of their formation and also for metastasis, which is another point where few cells resist our defenses.”

According to the authors, “By eliminating PGLYRP1 from tumor cells, we see that the immune system responds by attacking them, which prevents the formation of a primary tumor and the spread of these cells to form metastases.”

Experts are now developing treatments that will block or eliminate this protein, hoping to combine them with modern treatments and attack stem cells in a different way.