Myeloid derived suppressor cell depletion for the treatment of hepatoblastoma 4283

Abstract Description Introduction Hepatoblastoma (HB) is the most common form of liver cancer in childhood. Neutrophilic myeloid derived suppressor cells (PMN-MDSCs) are immunosuppressive cells recruited to liver tumors. Depletion of PMN-MDSCs has not been studied as immunotherapy for HB. Methods HB was induced in C57BL/6 or FVB/N mice using hydrodynamic tail vein injection of YAP and β-catenin plasmids. Anti-Ly6G, CXCR2 inhibitor (CXCR2i), and/or anti-PD1 were administered IP. Liver immune cells were isolated using density gradient centrifugation in Percoll. Results Anti-Ly6G administration caused a reduction in tumor weight, an increase in CD8+ T cells, an increase in the proliferation of CD8+T cells, and CD44+CD8+ activated T cells. Administering a combination of CXCR2i and anti-PD1 showed incomplete PMN-MDSC depletion, an increase in CD4+ T cells, an increase in activated CD44+CD4+ cells, and a decrease in frequency of naive CD4+CD62L+ cells, suggesting a helper T-cell driven antitumor response. Conclusion PMN-MDSC depletion has potential as a treatment for HB. We will further leverage this treatment strategy in combination with anti-PD1 checkpoint inhibition to assess its effect on HB. Funding Sources National Institute On Minority Health And Health Disparities of the National Institutes of Health under Award Number U54MD007601 (Ola HAWAII), The Chun Foundation, Andrew and Mary Weinberg Foundation Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)