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

• We examined role of HO1 in Treg survival in hypoxic condition.
• We analyzed role of HO1 inhibition in brain tumor model.
• HO1 preferentially protects Treg under hypoxic conditions.
• Tregs localize in close proximity to the hypoxic areas within brain tumors.
• SnPP decreases the number of Tregs and IL-10 production by the existing Tregs.

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 31 days (p < 0.05)). Thus HO1 inhibition provides another alternative way of therapeutically targeting Tregs in MG.