title: Critical Role of Tumor Microenvironment in Shaping NK Cell Functions: Implication of Hypoxic Stress.
abstract: Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells, a key component of the innate immunity, are recognized as potent anticancer mediators. Extensive studies have been detailed on how NK cells get activated and recognize cancer cells. In contrast, few studies have been focused on how tumor microenvironment-mediated immunosubversion and immunoselection of tumor-resistant variants may impair NK cell function. Accumulating evidences indicate that several cell subsets (macrophages, myeloid-derived suppressive cells, T regulatory cells, dendritic cells, cancer-associated fibroblasts, and tumor cells), their secreted factors, as well as metabolic components (i.e., hypoxia) have immunosuppressive roles in the tumor microenvironment and are able to condition NK cells to become anergic. In this review, we will describe how NK cells react with different stromal cells in the tumor microenvironment. This will be followed by a discussion on the role of hypoxic stress in the regulation of NK cell functions. The aim of this review is to provide a better understanding of how the tumor microenvironment impairs NK cell functions, thereby limiting the use of NK cell-based therapy, and we will attempt to suggest more efficient tools to establish a more favorable tumor microenvironment to boost NK cell cytotoxicity and control tumor progression.
authors.affiliation: INSERM U 1186, Equipe labellisée Ligue Contre le Cancer, Gustave Roussy Campus , Villejuif , France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Hasmim
authors.affiliation: INSERM U 1186, Equipe labellisée Ligue Contre le Cancer, Gustave Roussy Campus , Villejuif , France.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Messai
authors.affiliation: INSERM U 1186, Equipe labellisée Ligue Contre le Cancer, Gustave Roussy Campus , Villejuif , France.
authors.forename: Linda
authors.initials: L
authors.lastname: Ziani
authors.affiliation: INSERM U 1186, Equipe labellisée Ligue Contre le Cancer, Gustave Roussy Campus , Villejuif , France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Thiery
authors.affiliation: INSERM U 1186, Equipe labellisée Ligue Contre le Cancer, Gustave Roussy Campus , Villejuif , France ; Department of Hematology and Bone Marrow Transplantation, Gustave Roussy Campus , Villejuif , France.
authors.forename: Jean-Henri
authors.initials: JH
authors.lastname: Bouhris
authors.affiliation: INSERM U 1186, Equipe labellisée Ligue Contre le Cancer, Gustave Roussy Campus , Villejuif , France.
authors.forename: Muhammad Zaeem
authors.initials: MZ
authors.lastname: Noman
authors.affiliation: INSERM U 1186, Equipe labellisée Ligue Contre le Cancer, Gustave Roussy Campus , Villejuif , France.
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
keywords: HIF; immune suppression; microenvironment; natural killer cells; solid tumors