Blockade of suppressive myeloid cells is effective against neuroblastoma

Neuroblastoma (NB) is a challenging pediatric cancer with a 5-year survival rate below 50% in high-risk patients. Improvements were achieved with anti-GD2 therapies, but many patients still relapse. CD11b+ immune suppressive cells of myeloid lineage represent a promising target, as their immunosuppressive role in tumorigenesis was shown. Here, we analyzed myeloid-derived suppressor cells (MDSC) and the expression of MDSC-associated genes in a syngeneic NB mouse model. To show tumor promoting effects of CD11b+ cells and MDSC, these two cell populations were blocked by anti-CD11b monoclonal antibody administration or selectively depleted by low dose 5-Fluorouracil (5-FU) treatment, respectively. High numbers of CD11b+ leukocytes and a strong tumor-dependent induction of MDSC-associated genes could be shown by flow cytometry, immunohistochemical and RT-PCR analyses. MDSC depletion by both anti-CD11b and 5-FU treatment (superior effect) reduced the expression of MDSC-associated genes, delayed tumor growth and improved survival, suggesting a negative role of MDSC in NB. In conclusion, the depletion of immune suppressive myeloid cells resembles a promising treatment strategy against NB.