Strategy Revealed By Which Pancreatic Cancer’s Most Aggressive Cells Evade The Body’s Defenses – Responsible

He pancreas cancer It is usually detected in late stages and is very resistant to chemotherapy. Part of its aggressiveness is due to the fact that some of its cells, called cancer stem cells, are capable of restarting tumors and also evade 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 disguising themselves with a protein that normally serves to protect them.

This discovery may make it easier for immunotherapy-based treatments to be effective in pancreatic cancer. Susana García-Silva, researcher at the National Cancer Research Center (CNIO)“The challenge now is to block the protein we’ve identified and see if 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 tumor immune escape strategies, especially cancer stem cell strategies, since they are what support tumor growth.” García-Silva, from the Microenvironment and Metastasis Group at CNIO, is a co-author of this study, which used animal models and patient samples and was published in the journal Gut.

Co-authors also include Juan Carlos López-Gil from the Ramón y Cajal Institute for Medical Research (IRYCIS), the Autonomous University of Madrid (UAM) and the Solz Morreale Institute for Biomedical Research (IIBM-CSIC-UAM); Bruno Sainz from CIBERONC, IRYCIS and IIBM-CSIC-UAM; and Christopher Heeschen from the Candiolo Cancer Institute (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. 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 another task: to disguise themselves as cells of the defense system and thus camouflage themselves among the cells that should destroy them.

“It was already known that tumor cells use defense system proteins to camouflage themselves and escape.but the use of a protein with antibacterial properties as an immunoresistance strategy in cancer has 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 that these cells spread to form metastases,” says Sainz. “We are now developing treatments that will block or eliminate this protein, in the hope that we can combine them with current treatments and attack stem cells in a different way.”

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