Strategy that allows pancreatic cancer to ‘outsmart’ defenses

After decades of wanting to understand how they achieve this, Spanish research teams are now revealing their strategy: pancreatic cancer stem cells evading protective cells. changing clothes with a protein that usually serves for protection.

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 have identified 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 for pancreatic cancer,” Garcia-Silva explains. “For them to be effective in pancreatic cancer as well, we need to understand prevention strategies. immune escape tumors, especially cancer stem cells, since they are what support tumor growth.”

García-Silva, from the CNIO Microenvironment and Metastasis Group, is a co-author of the study, which used animal models and patient samples and was published in the journal. intestine.

They are also co-authors Juan Carlos Lopez-Gilfrom the Ramon y Cajal Institute for Medical Research (IRISIS), from the Autonomous University of Madrid (UAM) and the Solz Morreale Institute of Biomedical Research (IIBM-CSIC-UAM); Bruno Sainzfrom SIBERONK, from IRISIS and from IIBM-CSIC-UAM; And Christopher Heeschen from the Candiolo Cancer Institute (Moscow)IRCCS), in Italy, and former group leader at CNIO.

Antibacterial protein linked to cancer

The protein that pancreatic cancer stem cells use to protect themselves from host cells surprised Garcia-Silva. It’s called PGLYRP1 and belongs to a family of proteins found 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: wear suits cells of the defense system and thus camouflages itself precisely 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 Garcia-Silva.

New treatments in development

We now know that the role of PGLYRP1 in pancreatic cancer is “highly relevant,” the CNIO researcher points out. “If a pancreatic cancer cell is alone and has to resist the immune system, it needs this protein to evade it, grow and generate a tumor. “PGLYRP1 is important in the early stages of tumor formation, as well as for the formation of metastases, which is another case where few cells resist the immune system.”

“When we eliminate 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,” says Sainz. “We are now developing treatments that will block or eliminate this protein, in hopes of combining them with current treatments and attacking stem cells in a different way.”

Help Article:

Lopez-Gil JC, Garcia(1)Silva S, Ruiz-Cañas L, et al. Peptidoglycan recognition protein 1 imparts immune evasion properties to pancreatic cancer stem cells Gut. https://gut.bmj.com/content/early/2024/05/14/gutjnl-2023-330995

Fountain: TsNIO