title: Heme oxygenase-1 protects regulatory T cells from hypoxia-induced cellular stress in an experimental mouse brain tumor model.
abstract: Two characteristic features of malignant gliomas (MG) are the presence of hypoxia and accumulation of regulatory T cells (Tregs). Heme-oxygenase-1 (HO1) is a cytoprotective enzyme expressed in high level by Tregs in glioma. In this study, we show that higher HO1 expression in Tregs is associated with increased survival under hypoxic conditions and that HO1 inhibitor, tin protoporphyrin (SnPP), abrogates the survival benefits. Moreover, SnPP preferentially eliminates Tregs and treatment with SnPP of tumor bearing mice significantly increases survival (23 to 31days (p<0.05)). Thus HO1 inhibition provides another alternative way of therapeutically targeting Tregs in MG.
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Mahua
authors.initials: M
authors.lastname: Dey
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Chang
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Wainwright
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Atique U
authors.initials: AU
authors.lastname: Ahmed
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Balyasnikova
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL, USA. Electronic address: mlesniak@surgery.bsd.uchicago.edu.
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D011524:Protoporphyrins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology*; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1
keywords: Glioma; Heme oxygenase 1; Hypoxia; Immunization; Regulatory T cells; Tin protoporphyrin