Protein that helps pancreatic cancer cells evade immune system identified

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Washington, Jan 11 : Researchers at Jefferson's Kimmel Cancer Center in Philadelphia, have found that a protein that helps pancreatic cancer cells evade the immune system.

The protein, the researchers state, produced by metastatic cancer cells in the lymph nodes of patients with pancreatic cancer, do this by destroying the T-cells.

This protein called IDO (indolamine 2'3 dioxygenase) also aids in preventing a woman's body from rejecting a foetus. It prevents the pancreatic cancer cells from being detected by the immune system by allowing them to spread in the body.

When the pancreatic cells spread to the lymph nodes, it can be easily detected by the scientists and may have future implications in enhancing tumor immune therapy strategies against the fast-moving, deadly disease.

The study was led by Jonathan Brody, Ph.D., assistant professor of Surgery at Jefferson Medical College of Thomas Jefferson University.

He said that one mechanism through which metastatic cancer cells are able to survive in nearby lymph nodes, is by avoiding the immune system. IDO was also found to be critical to regulating the "immune environment."

The researchers wanted to find out whether metastatic pancreatic cancer cells residing in the lymph nodes expressed IDO to avoid being detected and then if it could be possible for them to target this enzyme with available drugs to prevent the cancer cells from hiding from the immune system.

The scientists examined IDO expression in 14 lymph nodes to which pancreatic cancer cells had spread and then they were compared to the primary tumors that had not spread in the same patients.

A greater expression of the IDO protein in the cancerous lymph nodes was found out in all the cases. Also, little IDO was found to be present in three cases of lymph node-negative pancreatic cancers.

It was already known that IDO shuts off tryptophan production in T-cells, putting them in a resting state, and recruits a different type of immune cell called T-regulatory cells, which can inhibit the immune system.

"These data point to the fact that IDO may play a role in helping cancer cells avoid the immune system," said Dr. Brody.

Pancreatic cancer cell lines were also examined in the laboratory for IDO expression. The scientists didn't find any IDO expression by using antibodies to IDO, until they treated the cells with interferon to ape the conditions in the lymph nodes. This enabled the tumor cells to make the enzyme.

"The immune system appears to have a balance that can allow cancer cells to grow but also can detect and destroy them. While IDO is crucial to regulating this balance, too much IDO tips the balance toward an immune suppression, supporting cancer growth," explained Brody.

The researchers also indicated that IDO inhibitors are available clinically, and theoretically could be used with chemotherapy or some other forms of immune therapy against pancreatic cancer.

The study's findings were presented at the recent meeting of the Southern Surgical Association in Hot Springs, VA and have been accepted for publication in the Journal of the American College of Surgeons.

ANI

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