Abstract: The present invention provides, among other things, methods and compositions for the treatment of cancer. The present invention is based, in part, on the surprising discovery that ablation of regulatory T cells (Treg), for example, transient ablation of Treg, is able to drastically reduce tumor burden and reduce metastasis when used as a single agent. In some embodiments, provided methods and compositions are used in combination with one or more other anti-tumor therapies, for example, ionizing radiation.