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. This evidence concerns the gene CD40 and neoplasm.