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J Neuroimmunol. 2014 Jan 15;266(1-2):33-42. doi: 10.1016/j.jneuroim.2013.10.012. Epub 2013 Nov 8.

Heme oxygenase-1 protects regulatory T cells from hypoxia-induced cellular stress in an experimental mouse brain tumor model.

Author information

1
The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
2
The Brain Tumor Center, The University of Chicago, Chicago, IL, USA. Electronic address: mlesniak@surgery.bsd.uchicago.edu.

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.

KEYWORDS:

Glioma; Heme oxygenase 1; Hypoxia; Immunization; Regulatory T cells; Tin protoporphyrin

PMID:
24268287
PMCID:
PMC3932190
DOI:
10.1016/j.jneuroim.2013.10.012
[Indexed for MEDLINE]
Free PMC Article
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