While the addition of CTLA-4 inhibition alone was not effective in N-MYC driven 9464D-GD2 mice, treatment with CpG, and anti-CD40 in addition to anti-CTLA-4, radiation, and the immunocytokine produced complete tumor regression in four of five mice, and increased macrophages and decreased Treg cells within the tumor microenvironment. The gene discussed is CTLA4; the disease is neoplasm.