Mitigating the prevalence and function of myeloid-derived suppressor cells by redirecting myeloid differentiation using a novel immune modulator.

Background: Immune suppression is common in neoplasia and a major driver is tumor-induced myeloid dysfunction. Yet, overcoming such myeloid cell defects remains an untapped strategy to reverse suppression and improve host defense. Exposure of bone marrow progenitors to heightened levels of myeloid growth factors in cancer or following certain systemic treatments promote abnormal myelopoiesis characterized by the production of myeloid-derived suppressor cells (MDSCs) and a deficiency in antigen-presenting cell function.

Cancer-induced systemic myeloid dysfunction: Implications for treatment and a novel nanoparticle approach for its correction.

Unlike other regulatory circuits, cancer-induced myeloid dysfunction involves more than an accumulation of impaired dendritic cells, protumoral macrophages, and myeloid derived suppressor cells in the tumor microenvironment. It is also characterized by "aberrant" myelopoiesis that results in the accumulation and expansion of immature myeloid precursors with a suppressive phenotype in the systemic circulation. The first part of this review briefly describes the evidence for and consequences of this systemic dysfunctional myelopoiesis and the possible reinforcement of this phenomenon by conventional treatments used in patients with cancer, in particular chemotherapy and granulocyte-colony stimulating factor.

Nimotuzumab Induces NK Cell Activation, Cytotoxicity, Dendritic Cell Maturation and Expansion of EGFR-Specific T Cells in Head and Neck Cancer Patients.

Survival benefit and long-term duration of clinical response have been seen using the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody (mAb) nimotuzumab. Blocking EGFR signaling may not be the only mechanism of action underlying its efficacy. As an IgG1 isotype mAb, nimotuzumab's capacity of killing tumor cells by antibody dependent cellular cytotoxicity (ADCC) and to induce an immune response in cancer patients have not been studied.