October 31, 2005 -- Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, have discovered a mechanism by which cancer patients' immune systems respond to chemotherapy. The new finding changes the current understanding of how the immune system responds to chemotherapy and could lead to opportunities for new treatments based on enhancing the body's immune response to the disease. The study findings appear in Nature Medicine*, November 2005

Chemotherapy for cancer is known to severely deplete the number of immune system T-cells -- creating a condition known as lymphopenia. Paradoxically, lymphopenia leads to increased immune system response It has not been clear how this happens. Some scientists have believed that chemotherapy-induced lymphopenia results in selective depletion of "suppressor" T-cells, a type of T-cell that acts to turn off or inhibit an immune response. Depletion of "suppressor" T-cells increases immune response in cancer patients. However, this new study indicates that even though chemotherapy depletes T-cells, it does not selectively destroy suppressor or regulatory T-cells, as previously assumed. Instead, the study showed that the lymphopenia condition caused by chemotherapy actually provided a good environment for proliferation of suppressor T-cells that are believed to contribute to the ability of tumors to evade the body's immune system. The mechanism by which this occurs is not entirely clear, but could involve interleukin-2 (IL-2), a cytokine which was not previously associated with suppressing immune responses.

Researchers at NCI's Center for Cancer Research (CCR), Pediatric Oncology Branch, examined immune recovery in 26 young cancer patients with pediatric sarcomas (highly malignant tumors) who received cyclophosphamide-based chemotherapy, which depleted lymphocytes. The patients were then infused with their own frozen lymphocytes, which had been stored before chemotherapy had begun. Researchers examined the impact of this treatment on the patients' immune recovery with or without recombinant IL-2, an agent that has been considered capable of restoring an immune system weakened by chemotherapy. The cancer patients in the study were assigned to one of three groups: the first group received moderate-dose IL-2 therapy; the second group received low-dose IL-2 treatment, and the third group received no IL-2. The researchers reported that the patients who received IL-2 -- at either dose -- showed a marked increase in suppressor T-cells after chemotherapy. These findings were confirmed in a parallel study in lymphopenic mice.

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