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Moffitt researchers say effective immunotherapy for melanoma hinges on blocking suppressive factors
Date:12/10/2012

Researchers at the Moffitt Cancer Center have found that delayed tumor growth and enhanced survival of mice bearing melanoma were possible by blocking the reconstitution of myeloid-derived suppressor cells and Tregs (suppressors of anti-tumor activity) after total body irradiation had eliminated them. Blocking myeloid-derived suppressor cells and regulatory T-cell reconstitution improved adoptive T-cell therapy, an immunotherapy designed to suppress tumor activity.

The study appears in the December issue of The Journal of Immunology.

"Melanoma is a leading cause of cancer mortality," said Shari Pilon-Thomas, Ph.D., assistant member of the Immunology Program at Moffitt. "With few nonsurgical options for treating melanoma, immunotherapy, which focuses on the induction of immunity against cancer cells, is a promising approach. However, a major hurdle in developing effective immunotherapies is tumor-induced suppression that can limit the effectiveness of tumor-specific T-cells used in immunotherapy."

Chemotherapy or radiation can induce lymphopenia, the condition of having an abnormally low level of white blood cells. This condition is optimal for adoptive T-cell therapeutic strategies. However, after the induction of lymphopenia, suppressor populations that favor tumor progression begin reconstitution, including regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSC). According to the researchers, tumor-induced suppression can stem from quickly reconstituted Tregs and MDSC.

This knowledge led to their research question, whether blocking the reconstitution of suppressor populations - such as Tregs and myeloid derived suppressor cells - could lead to better immunotherapy in mice bearing melanoma. Mice were treated with docetaxel, a chemotherapeutic drug that targets MDSC, followed by adoptive T cell therapy. In brief, the study demonstrated that when myeloid-derived suppressor cells and Treg reconstituti
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Contact: Kim Polacek
kim.polacek@moffitt.org
813-745-7408
H. Lee Moffitt Cancer Center & Research Institute
Source:Eurekalert

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