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.