A way to prevent pancreatic cancer from spreading post-surgery?

May 17, 2018, Cold Spring Harbor Laboratory
On the left is a section of a pancreatic cancer patient's primary tumor, with cancer cells (red) and CK19, a marker of proliferation (green), evident. On the right is a sample of the liver in the same patient revealed 27 isolated DCCs (disseminated cancer cells). These cells are dormant, but activate when T cell levels in the patient drop, as they do immediately following surgery. This provides a clue about how to avoid liver metastasis in pancreatic cancer patients who undergo surgery. Credit: Fearon Lab, CSHL

Scientists at Cold Spring Harbor Laboratory (CSHL) have solved a mystery about how pancreatic cancer spreads following surgery in patients whose tumor is successfully removed. After surgery, patients' typically experience a two-week period during which their immune system is depleted as a result of a surge in post-operative stress hormone (cortisol) levels. With killer T-cell levels sagging, isolated, dormant cancer cells that have already traveled to the liver and possibly other organs via the bloodstream begin to grow or metastasize.

This post-operative period, suggests CSHL Professor Douglas Fearon, "offers a window during which efforts might be made to keep cortisol levels down and T strong so the patient's own immune system can kill the cells that have made their way to other parts of the body but until this point have been dormant."

Surgery is usually not an option for pancreas cancer , since most are diagnosed after the has metastasized. This helps explain why only 8 percent of those diagnosed are still alive after 5 years. But doctors have been puzzled by the poor outcome in patients who should do better: the minority whose tumor seems confined to the pancreas at the time of diagnosis, and thus qualify for surgery. In many such patients, the , inspected during the operation, appears cancer-free. Yet within two years, most of these patients develop lethal metastatic cancer, often in the liver.

Today in Science a team led by Fearon and Dr. Arnaud Pommier in his lab, explains that are already in the liver well before patients have their primary tumor removed. They are likely carried there by the bloodstream, having been shed by the primary tumor. Fearon estimates that in a typical patient, 14 million cancer cells pass through the liver every day.

The immune system can kill most of the cancer cells deposited in the liver, but often it isn't completely effective. Fearon and others have discovered in recent years how the immune system can be tricked or hijacked by cancer cells. The new discovery is one example.

The immune system seeks out and destroys cancer cells by sensing proteins called MHC1 and CK19 that are present on the outer membranes of the cancer cells. Fearon's team found that the cancer cells that have been laying dormant in the liver of pancreatic cancer patients don't express these proteins so killer T cells can't find them. In situations such as post-operative surgical stress, where T cells in the liver are depleted, the dormant start to express MHC1 and CK19 markers again and begin to divide, becoming seeds of metastatic lesions.

Explore further: New receptor genes turn T-cells into powerful liver cancer foes

More information: "Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases" Science, science.sciencemag.org/cgi/doi … 1126/science.aao4908

Related Stories

New receptor genes turn T-cells into powerful liver cancer foes

April 3, 2018
Mouse genes that make human T cells powerful at fighting liver cancer could one day help patients do the same, scientists report.

Why cancer cells go to sleep—the mystery of cancer dormancy

April 27, 2018
Cancer has always been thought of as something that grows rapidly and uncontrollably, but this view may be wrong. New evidence suggests that cancer alternatively uses the "accelerator" and the "brake" in order to survive.

Metastatic cancer gorges on fructose in the liver

April 26, 2018
Biomedical engineers at Duke University have demonstrated that metastatic cancer cells can reprogram their metabolism to thrive in new organs. Specifically, the research shows that cells originating from colorectal cancer ...

Study suggests colon cancer cells carry bacteria with them when they metastasize

November 24, 2017
(Medical Xpress)—A team of researchers working at Harvard University has found evidence that suggests a certain type of bacteria found in colon cancer tumors makes its way to tumors in other body parts by traveling with ...

A new strategy for prevention of liver cancer development

November 14, 2017
Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective ...

Team finds a potentially better way to treat liver cancer

October 12, 2017
A Keck School of Medicine of USC research team has identified how cancer stem cells survive. This finding may one day lead to new therapies for liver cancer, one of the few cancers in the United States with an incidence rate ...

Recommended for you

Treatment shown to improve the odds against bone marrow cancer

December 15, 2018
Hope has emerged for patients with a serious type of bone marrow cancer as new research into a therapeutic drug has revealed improved outcomes and survival rates.

Immunotherapy combo not approved for advanced kidney cancer patients on the NHS

December 14, 2018
People with a certain type of advanced kidney cancer will not be able to have a combination of two immunotherapy drugs on the NHS in England.

New drug seeks receptors in sarcoma cells, attacks tumors in animal trials

December 13, 2018
A new compound that targets a receptor within sarcoma cancer cells shrank tumors and hampered their ability to spread in mice and pigs, a study from researchers at the University of Illinois reports.

Surgery unnecessary for many prostate cancer patients

December 13, 2018
Otherwise healthy men with advanced prostate cancer may benefit greatly from surgery, but many with this diagnosis have no need for it. These conclusions were reached by researchers after following a large group of Scandinavian ...

Lethal combination: Drug cocktail turns off the juice to cancer cells

December 12, 2018
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth—this was discovered by researchers from the University of Basel's Biozentrum two years ago. In a follow-up study, ...

Combining three treatment strategies may significantly improve melanoma treatment

December 12, 2018
A study by a team led by a Massachusetts General Hospital (MGH) investigator finds evidence that combining three advanced treatment strategies for malignant melanoma—molecular targeted therapy, immune checkpoint blockade ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.