Some Cancers Take Advantage of T-Reg Cells to 'Cloak' Themselves

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Tumor Wizardry Wards Off Attacks From The Immune System

7/13/2006

Source: Washington University School of Medicine

Like the fictional wizard Harry Potter, some cancerous tumors seem

capable of wrapping themselves in an invisibility cloak. Researchers

at Washington University School of Medicine in St. Louis have found

that pancreatic tumors hide from the body's immune surveillance by

surrounding themselves with cells that make it hard for the immune

system to detect them.

The tumor-protecting cells are white blood cells called regulatory T

cells, or T-reg for short. Under ordinary circumstances, T-reg cells

inhibit immune components responsible for killing unwanted cells --

this allows T-reg cells to help prevent autoimmune reactions.

The scientists discovered that cancerous cells take advantage of T-

reg cells' suppressor ability, enlisting them to keep the immune

system at bay. Their report appears in the July/August issue of the

Journal of Immunotherapy.

" Earlier, we found that T-reg cells are much more prevalent in

patients with breast cancer and pancreatic cancer than in healthy

patients, " says C. Linehan, M.D., associate professor of

surgery and a researcher with the Siteman Cancer Center. " The new

findings show that tumors are directly responsible for the increase

of T-reg cells and can attract T-reg cells to their vicinity. This

could be one way for tumors to evade immune surveillance. "

Linehan believes this could explain the failure of many experimental

anti-cancer vaccines. Such vaccines are designed to rev up the immune

response to cancer cells so that the immune system can attack tumors.

But a tumor shielded with T-reg cells could potentially circumvent

the immune system's attack and remain safe.

In mice implanted with pancreatic cancer, the researchers

demonstrated that tumor growth caused an increase in T-reg cells in

both the blood stream and in lymph nodes leading from the tumors.

When the research team blocked a signaling molecule that pancreatic

tumors secrete in abundance, T-reg cells were no longer present in

the tumor-draining lymph nodes, suggesting that this signaling

molecule, referred to as TGF-beta, has an important role in weaving a

tumor's cloak of invisibility. Such information could lead to a

method for blocking tumors from using T-reg cells for protection.

Other research by Linehan and colleagues showed that in mice with

pancreatic cancer, simply depleting T-reg cells slowed tumor growth

and increased survival time.

" We're looking at several potential ways to interfere with tumor

recruitment of T-reg cells, " Linehan says. " We'd like to see these

findings advance cancer immunotherapy. We want to find a way to

actively suppress T-reg cells and at the same time actively evoke an

immune response to tumor-specific antigens. "

In collaboration with other researchers at the School of Medicine,

Linehan is planning to set up a clinical trial that pairs T-reg

depletion with anti-cancer vaccine as a therapy for pancreatic cancer

patients.

" We're attacking the problem from different angles hoping to

translate these findings to our patients, " Linehan says. " Right now,

no effective treatment exists for pancreatic cancer. "