title: The Sabotaging Role of Myeloid Cells in Anti-Angiogenic Therapy: Coordination of Angiogenesis and Immune Suppression by Hypoxia.
abstract: Tumor angiogenesis has become a promising target for anti-tumor therapy. Unfortunately, the somewhat inevitable occurrence of resistance has limited the efficacy of anti-angiogenic therapy. In addition to their well-established role in immune suppression, bone marrow-derived myeloid cells actively contribute to tumor angiogenesis. More importantly, myeloid cells constitute one of the major mechanisms of resistance to angiogenesis inhibition. As the most pervasive feature in tumor microenvironment, hypoxia is able to initiate both pro-angiogenic and immunosuppressive capacities of myeloid cells. Tumor adapts to hypoxic stress primarily through signaling mediated by hypoxic inducible factors (HIFs) and consequently utilizes hypoxia to its own advantage. In this regard, hypoxia orchestrates both angiogenesis and immune evasion to support tumor growth. In this article, we will review available information on the sabotaging role of myeloid cells in anti-angiogenic therapy. We will also discuss how hypoxia coordinates the dual-role cellular and molecular participants in microenvironment to maximize the efficiency of angiogenesis and immunosuppression to promote tumor progression. J. Cell. Physiol. 232: 2312-2322, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Bazhin
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yuhui
authors.identifier: http://orcid.org/0000-0002-9320-2925
authors.initials: Y
authors.lastname: Yang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D058990:Molecular Targeted Therapy; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009389:Neovascularization, Pathologic; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D019139:Tumor Escape; D000072258:Tumor Hypoxia; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D020533:Angiogenesis Inhibitors; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012097:Repressor Proteins; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099162:Endothelial PAS Domain-Containing Protein 1; C116973:HIF3A protein, human; C467484:VEGFA protein, human; C000588866:KDR protein, human