When CTLA-4 and PD-1 are co-blocked in B16 melanoma cells vaccinated with B16-Flt3-ligand (Fvax), these agents synergistically increase the ratio of Teff to Treg and myeloid-derived suppressor cells, as well as the production of T cells that secrete IFN-γ and TNF-alpha. Here, TNF is linked to melanoma.