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      Hypoxia Promotes Tumor Growth in Linking Angiogenesis to Immune Escape

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          Despite the impressive progress over the past decade, in the field of tumor immunology, such as the identification of tumor antigens and antigenic peptides, there are still many obstacles in eliciting an effective immune response to eradicate cancer. It has become increasingly clear that tumor microenvironment plays a crucial role in the control of immune protection. Tumors have evolved to utilize hypoxic stress to their own advantage by activating key biochemical and cellular pathways that are important in progression, survival, and metastasis. Hypoxia-inducible factor (HIF-1) and vascular endothelial growth factor (VEGF) play a determinant role in promoting tumor cell growth and survival. Hypoxia contributes to immune suppression by activating HIF-1 and VEGF pathways. Accumulating evidence suggests a link between hypoxia and tumor tolerance to immune surveillance through the recruitment of regulatory cells (regulatory T cells and myeloid derived suppressor cells). In this regard, hypoxia (HIF-1α and VEGF) is emerging as an attractive target for cancer therapy. How the microenvironmental hypoxia poses both obstacles and opportunities for new therapeutic immune interventions will be discussed.

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          Most cited references 139

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            Myeloid-derived suppressor cells as regulators of the immune system.

            Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand during cancer, inflammation and infection, and that have a remarkable ability to suppress T-cell responses. These cells constitute a unique component of the immune system that regulates immune responses in healthy individuals and in the context of various diseases. In this Review, we discuss the origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit.
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              Type, density, and location of immune cells within human colorectal tumors predict clinical outcome.

              The role of the adaptive immune response in controlling the growth and recurrence of human tumors has been controversial. We characterized the tumor-infiltrating immune cells in large cohorts of human colorectal cancers by gene expression profiling and in situ immunohistochemical staining. Collectively, the immunological data (the type, density, and location of immune cells within the tumor samples) were found to be a better predictor of patient survival than the histopathological methods currently used to stage colorectal cancer. The results were validated in two additional patient populations. These data support the hypothesis that the adaptive immune response influences the behavior of human tumors. In situ analysis of tumor-infiltrating immune cells may therefore be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.

                Author and article information

                Front Immunol
                Front Immunol
                Front. Immun.
                Frontiers in Immunology
                Frontiers Research Foundation
                23 February 2012
                : 3
                1simpleINSERM U753, Institut Gustave Roussy Villejuif, France
                2simpleGénétique Oncologique, Ecole Pratique des Hautes Études, INSERM U753, Institut Gustave Roussy Villejuif, France
                3simpleDepartment of Medical Oncology, Institut Gustave Roussy Villejuif, France
                Author notes

                Edited by: Vincenzo Bronte, Immunology Unit, Italy

                Reviewed by: Antonio Sica, Università degli Studi del Piemonte Orientale Amedeo Avogadro, Italy; Suzanne Ostrand-Rosenberg, University of Maryland Baltimore County, USA; Andrea Facciabene, University of Pennsylvania, USA

                *Correspondence: Salem Chouaib, INSERM U753, Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France. e-mail: chouaib@

                This article was submitted to Frontiers in Tumor Immunity, a specialty of Frontiers in Immunology.

                Copyright © 2012 Chouaib, Messai, Couve, Escudier, Hasmim and Noman.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

                Figures: 1, Tables: 0, Equations: 0, References: 137, Pages: 10, Words: 9970
                Review Article


                hifα, angiogenesis, hypoxia, tumor progression, immune tolerance


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