As treatment with GSNO alone expands both activated DCs and CTLA-4-expressing immunosuppressive cells, the combinational use of antagonistic aCTLA-4 mAb with NO-donor GSNO results in synergistic and systemic anticancer effects in a melanoma tumor model resistant to either GSNO or aCTLA-4 administered systemically as monotherapies. The gene discussed is CTLA4; the disease is neoplasm.