Provided are methods of reducing the size of a tumor or inhibiting the growth of cancer cells in an individual or inhibiting the development of metastatic cancer by administering an effective amount of a soluble form of a co-stimulatory molecule from an antigen presenting cell and by reducing the activity of immunoregulatory T cells in the individual. Methods of reduction in the activity of immunoregulatory T cells involve removing them ex vivo or depleting or inactivating them in vivo. Also provided are cancer therapeutic compositions comprising a soluble form of a co-stimulatory molecule from an antigen presenting cell and an antibody specific for an intracellular antigen.