MYC, a transcription factor, regulates the expression of immune checkpoint proteins CD47 and PD-L1 on tumor cells, which influence the anti-tumor immune response. In mouse and human tumor models, suppression of MYC leads to reduced levels of CD47 and PD-L1, enhancing anti-tumor immunity. Conversely, inactivation of MYC in tumors with high CD47 or PD-L1 expression suppresses immune responses and allows tumor growth. MYC binds directly to the promoters of CD47 and PD-L1 genes, regulating their expression. MYC inactivation promotes tumor regression by recruiting immune cells and inducing apoptosis, while also inhibiting tumor angiogenesis and inducing cell senescence. CD47 and PD-L1 act as "don't eat me" and "don't find me" signals, respectively, to evade immune detection. Therapeutic suppression of these proteins has shown promise in clinical trials. MYC overexpression may contribute to immune evasion by upregulating CD47 and PD-L1, while its inactivation restores immune surveillance. This study highlights the role of MYC in modulating immune regulatory molecules, which is critical for tumor initiation and maintenance. The findings suggest that targeting MYC or its downstream effectors could be a promising strategy for cancer immunotherapy.MYC, a transcription factor, regulates the expression of immune checkpoint proteins CD47 and PD-L1 on tumor cells, which influence the anti-tumor immune response. In mouse and human tumor models, suppression of MYC leads to reduced levels of CD47 and PD-L1, enhancing anti-tumor immunity. Conversely, inactivation of MYC in tumors with high CD47 or PD-L1 expression suppresses immune responses and allows tumor growth. MYC binds directly to the promoters of CD47 and PD-L1 genes, regulating their expression. MYC inactivation promotes tumor regression by recruiting immune cells and inducing apoptosis, while also inhibiting tumor angiogenesis and inducing cell senescence. CD47 and PD-L1 act as "don't eat me" and "don't find me" signals, respectively, to evade immune detection. Therapeutic suppression of these proteins has shown promise in clinical trials. MYC overexpression may contribute to immune evasion by upregulating CD47 and PD-L1, while its inactivation restores immune surveillance. This study highlights the role of MYC in modulating immune regulatory molecules, which is critical for tumor initiation and maintenance. The findings suggest that targeting MYC or its downstream effectors could be a promising strategy for cancer immunotherapy.