Tumor Cells May Use T-Reg Cells to Escape Detection

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Tumor Wizardry Wards Off Attacks From The Immune System

ScienceDaily (Jul. 13, 2006) — 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. "

Liyanage Uk, Goedegebuure PS, TT, Viehl CT, Moo-Young TA, Larson

JW, Frey DM, Ehlers JP, Eberlein TJ, Linehan DC. Increased prevalence

of regulatory T cells (T-reg) is induced by pancreas adenocarcinoma.

Journal of Immunotherapy July/August 2006;26(4):416-424.

Funding from the National Cancer Institute and the National Institutes

of Health supported this research.

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Adapted from materials provided by Washington University School of

Medicine.

http://www.sciencedaily.com/releases/2006/07/060713154003.htm