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 reconstitution are blocked, immunotherapy with adoptive T cell transfer is more effective.
"It was important to understand the role of these suppressor populations after the induction of lymphopenia so that we can design more effective immunotherapeutic treatments for melanoma aimed at achieving complete tumor regression," concluded Dr. Pilon-Thomas.
About Moffitt Cancer Center
Located in Tampa, Moffitt is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt's excellence in research, its contributions to clinical trials, prevention and cancer control. Since 1999, Moffitt has been listed in U.S. News & World Report as one of "America's Best Hospitals" for cancer. With more than 4,200 employees, Moffitt has an economic impact on the state of nearly $2 billion. For more information, visit MOFFITT.org, and follow the Moffitt momentum on Facebook, twitter and YouTube.
Media release by Florida Science Communications
Journal
The Journal of Immunology