"This is a surprising result, since IL-2 has been considered an immune activator -- not a suppressor," commented Crystal L Mackall, M.D., head of CCR's Pediatric Oncology Branch Immunology Section and study co-author. "These results suggest that a large portion of IL-2's effects is to suppress immune responses." If, instead, a way could be designed to deplete the number of suppressor T-cells, that could create a chance for a different type of T-cell -- that attacks cancer cells -- to increase their numbers to fight the disease, she added.

Such an opportunity may exist, as the researchers also discovered that the suppressor T-cells that appeared following chemotherapy and IL-2 administration were derived from existing T-cells, rather than being created anew in the patients' thymus glands, where T-cells typically originate. As a result, "if one could deplete suppressor cells from the patient's system, these cells would not be efficiently regenerated," Mackall explained. "If a patient with lymphocyte depletion were also depleted of suppressor cells, the immune system would be predicted to be highly reactive -- and responsive to antitumor vaccines -- and therefore may be better able to fight cancer."


The study has important implications for developing future immunotherapies against cancer, as many researchers are interested in manipulating suppressor cells to make the immune system more effective in responding to cancer. "This study provides the first insight into what makes regulatory T-cells tick and therefore provides ideas for new ways to deplete or manipulate these cells more effectively in humans," Mackall added.

CCR's Pediatric Oncology Branch is planning a follow-up clinical trial that will attempt to rebuild the immune system in a similar set of patients who are depleted of suppressor T-cells and also will be administered a tumor vaccine. "We hope that this setting will lead to very vigorous antitumor immune responses that can prevent tumor recurrence," Mackall said.

For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4 CANCER (1-800-422-6237).

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

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