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Aggressive Immune Response Helps Colorectal Cancer Patients

The discovery may lead to more effective treatments, researchers say

WEDNESDAY, Dec. 21, 2005 (HealthDay News) -- European researchers have discovered one of the reasons why some colorectal cancers are more aggressive and likely to spread than others.

The reason is that in some people, the body's immune system mounts an effective defense against the tumor and against the tumor's attempt to spread to other sites in the body.

The anti-tumor cells generated by the immune system are called "effector memory T cells."

"Effector memory T cells have the capacity to recognize and kill tumor cells. These cells, located in the tumor, have a long-lasting anti-tumor activity, persist within the body and destroy distant tumor cells," said one of the study's authors, Jerome Galon, a research scientist at the French National Institute of Health and Medical Research in Paris.

Results of the study appear in the Dec. 22 issue of the New England Journal of Medicine.

More than 140,000 new cases of colorectal cancer are diagnosed each year in the United States, according to the American Cancer Society (ACS). The disease is responsible for about 56,000 deaths each year, making it the nation's second-leading cause of cancer death, according to the ACS.

Because little is known about how the immune system responds when cancers begin to spread, Galon and his colleagues analyzed the immune response to colorectal cancer tumor samples from 959 people.

The researchers looked for evidence of early metastasis, or spreading, of the cancer. Early signs of metastasis include blood vessel blockages, invasion of the lymphatic system and infiltration of the nerves. Together, the researchers collectively referred to these signs as VELIPI. VELIPI-positive cancers were those that were already spreading to other sites throughout the body.

After identifying each tumor as VELIPI-positive (257) or VELIPI-negative (702), the researchers then compared the groups to see if there were any differences.

There were. People with VELIPI-negative tumors were more likely to have a higher density of effector memory T cells, and they were more likely to live longer. On average, those with VELIPI-negative tumors lived 35 months, compared to 16.3 months for those with VELIPI-positive tumors.

"Effector memory T cells have a major impact on colorectal cancer evolution. These cells prevent tumor dissemination within the body and distant metastasis, and improve survival of the patients," said Galon.

Galon said these T cells kill tumor cells that attempt to migrate from the original tumor.

"The immune system, under appropriate conditions, may be effective in controlling or limiting cancer spread if the appropriate number and quality of immune cells can be mobilized by the first tumor site," said Dr. Giorgio Parmiani, chairman of the unit of immunotherapy of human tumors and the department of innovative therapies at Istituto Nazionale Tumori in Milan, Italy. Parmiani wrote an accompanying editorial in the same issue of the journal.

Galon said these findings could eventually help classify and "stage" tumors, giving doctors a better way to predict the course a cancer might take. In the long-term, he added, these findings could help lead to the development of an immunotherapy that could boost the immune response, especially that of the effector memory T cells, to more effectively fight colorectal cancer.

More information

To learn more about colon cancer, visit the American Gastroenterological Association.

SOURCES: Jerome Galon, Ph.D., research scientist, French National Insitute of Health and Medical Research (INSERM), Paris; Giorgio Parmiani, M.D., director, unit of immunotherapy and human tumors, and the department of innovative therapies, Istituto Nazionale Tumori, Milan, Italy; Dec. 22, 2005, New England Journal of Medicine
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