In summary, our study demonstrated that PepO, as a high level of biosafe immunomodulatory molecule, switches TAM from the tumor-promoting M2 to tumor-inhibitory M1 phenotype by interacting with TLR2 and TLR4 and activating PI3K-AKT-mTOR and inhibiting JAK2-STAT3 pathway. Here, AKT1 is linked to neoplasm.