EXOSOMES FROM CT26 CELLS PROMOTE TUMOR PROGRESSION BY SUBVERTING MACROPHAGE FROM M1 TO M2 MEDIATED PARTIALLY BY INTERLEUKIN-4

Background: Macrophages are a critical component of anti-tumor immunity but may be subverted from M1 phenotype, which mediates tumor elimination, to an alternatively – activated, M2 phenotype, which promotes tumor progression. Methodology: In this study, exosomes purified from CT26 cells culture medium were used to treat CT26 tumor – bearing mice. Then the polarization of macrophage from Balb/c mice was tested after incubation with exosomes by detection of Tumor Necrosis Factor-α (TNF-α), interleukin 6, 10 (IL6, IL10) and Chemokine (C-C motif) ligand 1 (CCL1) using ELISA assays and demonstrated that CT26 – derived exosomes effectively promote polarization of macrophage in vitro. IL4 is a strong inducer of M2 polarization, so we next measured the secretion of IL4 from macrophage after treating with exosomes and results showed that the expression of IL4 was dramatically elevated by CT26 – derived exosomes. Results: This result was confirmed by treating macrophages from IL-4 knockout mice in vitro and in vivo. Conclusion: Collectively, we suggest a novel mechanism by which CT26 – derived exosomes exert tumor promotion activity via subverting phenotype of macrophage.