Situational aldehyde dehydrogenase expression by regulatory T cells may explain the contextual duality of cyclophosphamide as both a pro-inflammatory and tolerogenic agent.

In two recent publications, we demonstrated that after allogeneic stimulation, regulatory T cells (Tregs) increase expression of aldehyde dehydrogenase (ALDH), the major in vivo mechanism of cyclophosphamide detoxification, thereby becoming cyclophosphamide resistant. Differential ALDH expression may explain why cyclophosphamide has pro- and anti-inflammatory effects that are temporally and contextually dependent.