Myeloid-derived suppressor cells (MDSCs) contribute to tumor-mediated immune escape and negatively correlate with overall survival of cancer patients. Nowadays, a variety of methods to target MDSCs are being investigated. Based on the intervention stage of MDSCs, namely development, expansion and activation, function and turnover, these methods can be divided into: (I) prevention or differentiation to mature cells, (II) blockade of MDSC expansion and activation, (III) inhibition of MDSC suppressive activity or (IV) depletion of intratumoral MDSCs. This review describes effective mono- or multimodal-therapies that target MDSCs for the benefit of cancer treatment.
Keywords: 5-FU, 5-fluorouracil; 5-Fluorouracil; ADAM17, metalloproteinase domain-containing protein 17; APCs, antigen presenting cells; ARG1, arginase-1; ATRA, all-trans retinoic acid; CCL2, chemokine (C-C motif) ligand 2; CD62L, L-selectin; CDDO-Me, bardoxolone methyl; COX2, cyclooxygenase 2; CTLs, cytotoxic T lymphocytes; CXCL12, chemokine (C-X-C motif) ligand 12; CXCL15, chemokine (C-X-C motif) ligand 15; DCs, dendritic cells; ERK1/2, extracellular signal-regulated kinases; Flt3, Fms-like tyrosine kinase 3; FoxP3, forkhead box P3; GITR, anti-glucocorticoid tumor necrosis factor receptor; GM-CSF/CSF2, granulocyte monocyte colony stimulating factor; GSH, glutathione; HIF-1α, hypoxia inducible factor 1α; HLA, human leukocyte antigen; HNSCC, head and neck squamous cell carcinoma; HPV-16, human papillomavirus 16; HSCs, hematopoietic stem cells; ICT, 3, 5, 7-trihydroxy-4′-emthoxy-8-(3-hydroxy-3-methylbutyl)-flavone; IFNγ, interferon γ; IL-10, interleukin 10; IL-13, interleukin 13; IL-1β, interleukin 1 β; IL-4, interleukin 4; IL-6, interleukin 6; IMCs, immature myeloid cells; JAK2, Janus kinase 2; MDSCs, myeloid-derived suppressor cells; MMPs, metalloproteinases (e.g., MMP9); Myd88, myeloid differentiation primary response protein 88; NAC, N-acetyl cysteine; NADPH, nicotinamide adenine dinucleotide phosphate-oxidase NK cells, natural killer cells; NO, nitric oxide; NOHA, N-hydroxy-L-Arginine; NSAID, nonsteroidal anti-inflammatory drugs; ODN, oligodeoxynucleotides; PDE-5, phosphodiesterase type 5; PGE2, prostaglandin E2; RNS, reactive nitrogen species; ROS, reactive oxygen species; SCF, stem cell factor; STAT3, signal transducer and activator of transcription 3; TAMs, tumor-associated macrophages; TCR, T cell receptor; TGFβ, transforming growth factor β; TNFα, tumor necrosis factor α; Tregs, regulatory T cells; VEGFR, vascular endothelial growth factor receptor; WA, withaferin A; WRE, Withaferin somnifera; all-trans retinoic acid; bisphosphonates; c-kit, Mast/stem cell growth factor receptor; gemcitabine; iNOS2, inducible nitric oxid synthase 2; immune suppressive mechanisms; mRCC, metastatic renal cell carcinoma; myeloid-derived suppressor cells; sunitinib therapeutic vaccination.