The dark side of cyclophosphamide: cyclophosphamide-mediated ablation of regulatory T cells.

Cancer immune escape is frequently associated with the induction of an inappropriate immune response, i.e., a response that does not inhibit but perhaps even promotes the tumor. Indeed, increased frequencies of tumor-infiltrating regulatory T cells (Tregs) are associated with an impaired prognosis in several cancers. Thus, depletion of Tregs, e.g., by cyclophosphamide, was proposed as a means to boost immune responses to cancer. In the present issue of the Journal, Sevko et al., however, provide evidence that cyclophosphamide exerted the unexpected effect of induction of myeloid-derived suppressor cells.