Rebecca Dodd, PhD, assistant professor in Hematology, Oncology, and Blood and Marrow Transplantation, received a three-year $811,125 grant from the US Department of Defense (DOD). Titled “Targeting a pro-tumorigenic immunosuppressive loop in MPNST,” Dodd’s project will examine the processes behind Malignant Peripheral Nerve Sheath Tumor (MPNST) development.
MPNSTs are sarcomas that occur in 8-13% of patients who develop Neurofibromatosis Type 1, a syndrome caused by mutations in the neurofibromin protein (NF1). However, Dodd says there is still a critical gap in researchers’ understanding of the immune cell function in MPNSTs.
“The 5-year survival rate for MPNSTs is less than 50%, and new treatment options are desperately needed,” Dodd said. “The NF1 mutations in the microenvironment alter the tumor immune landscape, and immunosuppressive cells are abundant in neurofibromin patient tumors.”
Dodd’s previous research identified the influence of mast cells in MPNST tumor growth. The results found that elimination of mast cells can slow tumor growth in people with MPNSTs, and these cells may offer new treatment options. Her team also found a connection between neurofibromin-mutant mast cells, T cells, and tumor cells that could be encouraging MPNST development. This new project will further investigate the implications of this immunosuppressive loop on MPNST growth.
“If successful, this proposal will identify specific molecular targets in the immune system that will slow the growth of MPNSTs,” Dodd said. “There is strong clinical rationale for targeting immunosuppressive cells in MPNSTs, since this strategy can improve response to conventional chemotherapies and checkpoint blockade immunotherapies in other cancers.”
Dodd is already very familiar with MPNST research. In 2019, she received a four-year, $792,000 Research Scholar grant from the American Cancer Society to investigate the biological mechanisms behind MPNST metastasis. This latest grant is her second DOD award; in 2018, she was awarded an NF1 New Investigator Award to study the mechanisms of myeloid cell function in MPNSTs.