We found that cryo-thermal-induced macrophage polarization toward the M1 phenotype was exclusively responsible for subsequent DC maturation, differentiation of CD4+ T cells to Th1 and cytotoxic T cells (CTLs), and generation of cytotoxic CD8+ T cells, which in turn was crucial for mediating cryo-thermal-induced long-term anti-tumor memory. Here, CD4 is linked to neoplasm.