Fig. 2

Three main strategies of targeting myeloid cells in neuroblastoma. Myeloid cells can be 1.) engaged as effector cells of immunotherapy via ADCC. 2.) removed from the TME by depletion with antibodies (anti-CD11b, anti-CD105, anti-CD33, or anti-CSF-1R) or myoablative chemotherapy. Additionally, myeloid cells can be depleted via inhibition of cytokines via IL6R blockade, or inhibition of TGFβ or STAT3. Finally, their recruitment can be blocked with CCR2 inhibitors, or anti-CCL2 or anti- TGFβ. 3.) reprogrammed to an anti-tumor, immunostimulatory phenotype, leading to reactivation of T cells. Myeloid cell reprogramming can be achieved by inducing epigenetic modifications, inhibiting cytokines and chemokines, suppressing COX activity, stimulating CD40 ligation, and preventing arginine uptake. Abbreviations: ADCC = antigen-dependent cellular cytotoxicity, Arg-1 = arginase-1, CCL2 = C–C motif chemokine ligand 2, CCR2 = CCL2 receptor, COX = cyclooxygenase, CSF-1R = colony stimulating factor 1 receptor, FcγRs = Fc gamma receptors, IFNγ = interferon gamma, ROS = reactive oxygen species, TGFβ = transforming growth factor beta, TME = tumor microenvironment, TNFα = tumor necrosis factor alpha, VEGF = vascular endothelial growth factor