title: Microenvironmental hypoxia orchestrating the cell stroma cross talk, tumor progression and antitumor response.
abstract: Hypoxia, a common feature of solid tumors and one of the hallmarks of tumor microenvironment, favors tumor survival and progression. Although hypoxia has been reported to play a major role in the acquisition of tumor resistance to cell death, the molecular mechanisms that control the survival of hypoxic cancer cells and the role of hypoxic stress in shaping the cross talk between immune cells and stroma components are not fully elucidated. Recently, several lines of investigation are pointing to yet another ominous outcome of hypoxia in the tumor microenvironment involving suppression of antitumor immune effector cells and enhancement of tumor escape from immune surveillance. Although the identification of tumor-associated antigens provided a new arsenal of approaches to enhance antigen-specific response, the immunotherapy approaches that are currently used in the clinic have only limited success. In fact, tumor stroma components including hypoxia are engaged in an active molecular cross talk that has serious implications for immunological recognition of tumor in shaping the microenvironment. In this review, we will focus on the impact of hypoxia on the regulation of the antitumor response and the subsequent tumor progression. We will also in particular discuss data that indicate that manipulation of hypoxic stress may represent an innovative strategy for a better immunotherapy of cancer.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 753, Villejuif, France.
authors.forename: Muhammad Zaeem
authors.initials: MZ
authors.lastname: Noman
authors.forename: Yosra
authors.initials: Y
authors.lastname: Messai
authors.forename: Thibault
authors.initials: T
authors.lastname: Carré
authors.forename: Intissar
authors.initials: I
authors.lastname: Akalay
authors.forename: Marine
authors.initials: M
authors.lastname: Méron
authors.forename: Bassam
authors.initials: B
authors.lastname: Janji
authors.forename: Meriem
authors.initials: M
authors.lastname: Hasmim
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D015687:Cell Hypoxia / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D000860:Hypoxia / Q000276:immunology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007157:Immunologic Surveillance; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D014411:Neoplastic Stem Cells; D015398:Signal Transduction; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D019139:Tumor Escape / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000099162:Endothelial PAS Domain-Containing Protein 1