Interestingly, PepO was not able to activate the PI3K-AKT pathway of M2 macrophages and not able to increase iNOS mRNA or protein expression in TLR4-deficient M2 BMDM and did not increase mRNA levels of CD86, IL-1β and IL-12a (Fig. 5A and Additional file 1: Fig S5A), which indicated that PepO could not switch TLR4−/− M2 BMDM toward the anti-tumor M1 phenotype. Here, TLR4 is linked to neoplasm.