title: Mechanisms of hypoxia-mediated immune escape in cancer.
abstract: An important aspect of malignant progression is the acquired ability of tumor cells to avoid recognition and destruction by the immune system (immune escape). Clinical cancer progression is also associated with the development of tumor hypoxia, which is mechanistically linked to the acquisition of malignant phenotypes in cancer cells. Despite the well-established role of hypoxia in tumor cell invasion and metastasis, and resistance to therapy, relatively few studies have examined the contribution of hypoxia to cancer immune escape. Accumulating evidence reveals that hypoxia can impair anticancer immunity by altering the function of innate and adaptive immune cells and/or by increasing the intrinsic resistance of tumor cells to the cytolytic activity of immune effectors. Here, we discuss certain aspects of the contribution of hypoxia to tumor immune escape and provide evidence for a novel role of cyclic guanosine monophosphate (cGMP) signaling in the regulation of hypoxia-induced immune escape. Thus, we propose that activation of cGMP signaling in cancer cells may have important immunotherapeutic applications.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University Kingston, Ontario, Canada. Department of Pathology and Molecular Medicine, Queen's University Kingston, Ontario, Canada.
authors.forename: Ivraym B
authors.initials: IB
authors.lastname: Barsoum
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University Kingston, Ontario, Canada.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Koti
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University Kingston, Ontario, Canada. Department of Urology, Queen's University Kingston, Ontario, Canada.
authors.forename: D Robert
authors.initials: DR
authors.lastname: Siemens
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University Kingston, Ontario, Canada. Department of Urology, Queen's University Kingston, Ontario, Canada. grahamc@queensu.ca.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Graham
mesh_terms: D056704:Adaptive Immunity; D015687:Cell Hypoxia / Q000235:genetics / Q000276:immunology*; D006152:Cyclic GMP / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D015398:Signal Transduction / Q000235:genetics; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology
chemical_list: D006152:Cyclic GMP