title: Heme oxygenase and carbon monoxide as an immunotherapeutic approach in transplantation and cancer.
abstract: Heme oxygenases (HOs) are the rate-limiting intracellular enzymes that degrade heme into carbon monoxide (CO), biliverdin and free divalent iron. Among HOs, HO-1 is the only isoform that is highly inducible in response to numerous stress factors and proinflammatory cytokines. This enzyme has shown cytoprotective, antioxidant and anti-inflammatory properties. Moreover, HO-1 and, in particular, CO also have tolerogenic actions in adaptive immune responses. HO-1 can provide immunosuppression through its expression by regulatory T cells or antigen-presenting cells. The physiological importance of HO-1 has been demonstrated in both mice and humans, and modulation of HO-1 expression has therapeutic effects in a variety of disorders involving inflammation and immune responses, including organ transplantation and cancer. Consistently, upregulation of the HO-1 pathway has a significant protective effect against spontaneous or induced autoimmune diseases, allergy and can be beneficial to graft survival. However, HO-1 may also play a role in tumorigenesis by lowering antitumor innate immune responses that control tumor growth or reduce tumor expansion. Thus, controlling HO-1 expression may be of great interest in immune intervention protocols where tolerance is desirable, such as in transplantation, or where enhanced immunogenicity is needed in the case of cancer.
authors.affiliation: ONIRIS, UMR_A 707, Nantes, F-44300, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Simon
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
authors.forename: Philippe
authors.initials: P
authors.lastname: Blancou
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases; D002248:Carbon Monoxide / Q000276:immunology*; D045142:Cross-Priming; D019610:Cytoprotection; D051547:Heme Oxygenase-1 / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D007249:Inflammation; D051379:Mice; D009369:Neoplasms; D016377:Organ Transplantation; D018384:Oxidative Stress / Q000276:immunology
chemical_list: D002248:Carbon Monoxide; D051547:Heme Oxygenase-1