Our investigation on immune resistance mechanisms that may underline the limited B16F10 tumor reduction driven by neoepitope vaccination demonstrated that the favorable immune changes of NK-cell enrichment and MDSC reduction in the tumor microenvironment (TME) occur in an immune-deserted environment, with limited T-cell infiltration and strong enrichment of regulatory FoxP3+ CD4+ T cells. The gene discussed is CD4; the disease is neoplasm.