Figures & data
Table I. Immunosuppressive effects of the hypoxic tumour microenvironment.
Table II. Heat-induced changes in tumour oxygenation.
Siemens DR, Hu N, Sheikhi AK, Chung E, Frederiksen LJ, Pross H, Graham CH. Hypoxia increases tumor cell shedding of MHC class I chain-related molecule: Role of nitric oxide. Cancer Res 2008; 68: 4746–4753 Yang M, Ma C, Liu S, Sun J, Shao Q, Gao W, Zhang Y, Li Z, Xie Q, Dong Z, et al. Hypoxia skews dendritic cells to a T helper type 2-stimulating phenotype and promotes tumour cell migration by dendritic cell-derived osteopontin. Immunology 2009; 128: eS237–S249 Panther E, Corinti S, Idzko M, Herouy Y, Napp M, la Sala A, Girolomononi G, Norgauer J. Adenosine affects expression of membrane molecules, cytokine and chemokine release, and the T-cell stimulatory capacity of human dendritic cells. Blood 2003; 101: 3985–3990 Zuckerberg AL, Goldberg LI, Lederman HM. Effects of hypoxia on interleukin-2 mRNA expression by T lymphocytes. Crit Care Med 1994; 22: 197–203 Conforti L, Petrovic M, Mohammad D, Lee S, Ma Q, Barone S, et al. Hypoxia regulates expression and activity of Kv1.3 channels in T lymphocytes: A possible role in T cell proliferation. J Immunol 2003; 170: 695–702 Caldwell CC, Kojima H, Lukashev D, Armstrong J, Farber M, Apasov SG, Sitkovsky MV. Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions. J Immunol 2001; 167: 6140–6149 Sitkovsky MV. T regulatory cells: Hypoxia-adenosinergic suppression and re-direction of the immune response. Trends Immunol 2009; 30: 102–108 Kim HP, Leonard WJ. CREB/ATF-dependent T cell receptor-induced Foxp3 gene expression: A role for DNA methylation. J Exp Med 2007; 204: 1543–1551 Ben-Shoshan J, Maysel-Auslender S, Mor A, Keren G, George J. Hypoxia controls CD4+CD25+ regulatory T-cell homeostasis via hypoxia-inducible factor-1alpha. Eur J Immunol 2008; 38: 2412–2418 Murdoch C, Giannoudis A, Lewis CE. Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood 2004; 104: 2224–2234 Grimshaw MJ, Balkwill FR. Inhibition of monocyte and macrophage chemotaxis by hypoxia and inflammation–A potential mechanism. Eur J Immunol 2001; 31: 480–489 Bosco MC, Reffo G, Puppo M, Varesio L. Hypoxia inhibits the expression of the CCR5 chemokine receptor in macrophages. Cell Immunol 2004; 228: 1–7 Nizet V, Johnson RS. Interdependence of hypoxic and innate immune responses. Nat Rev Immunol 2009; 9: 609–606 Bicher HI, Hetzel FW, Sandhu TS, Frinak S, Vaupel P, O'Hara MD, O'Brien T. Effects of hyperthermia on normal and tumor microenvironment. Radiology 1980; 137: 523–530 Tanaka K, Hasegawa T, Murata T, Sawada S, Akagi K. Effects of hyperthermia combined with radiation on normal and tumor microcirculation. Proceedings of the International Conference on Cancer Therapy by Hyperthermia Radiation and Drugs. Mag Bros, Tokyo 1982; 95–109 Vaupel P, Muller-Klieser W, Otte J, Manz R. Impact of various thermal doses on the oxygenation and blood flow in malignant tumors upon localized hyperthermia. Adv Exp Med Biol 1984; 169: 621–629 Okajima K, Griffin RJ, Iwata K, Shakil A, Song CW. Tumor oxygenation after mild-temperature hyperthermia in combination with carbogen breathing: Dependence on heat dose and tumor type. Radiat Res 1998; 149: 294–299 Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Dodge RK, Charles HC, Samulski TV, Prosnitz LR, Dewhirst MW. Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas. Cancer Res 1996; 56: 5347–5350