Suppression of tumor growth by a M2b macrophage reverter in humanized murine chimeras created with peripheral blood monocytes of patients with advanced stage hepatocellular carcinoma (TUM6P.967)

Abstract

Abstract Previously, we have reported that humanized murine chimeras created with peripheral blood monocytes from patients with early stage hepatocellular carcinoma (E-hccM) are resistant against tumor inoculation, while tumors grow in the same chimeras created with advanced stage patient monocytes (A-hccM). A majority of E-hccM are shown to be M1 monocytes, and a predominance of M2b monocytes is shown in A-hccM. In this study, we tried to suppress tumor growth in humanized chimeras created with A-hccM by CCL1 antisense ODN treatment, which reverts Mf from M2b to resident. Chimeras, created in X-irradiated NSG mice after inoculation of A-hccM (i.v., 1 x 106 cells/mouse, every 2 weeks), were inoculated with HepG2 cells (2 x 106 cells/mouse, s.c.). CCL1 antisense ODN (6 mg/mouse) were administered 4 times within 36 hrs of each A-hccM inoculation. In the results, 843 ± 227 mm3 of tumors were detected in the chimeras inoculated with A-hccM 8 weeks after the tumor inoculation, while tumors were not demonstrated in A-hccM chimeras treated with CCL1 antisense ODN, and 753 ± 165 mm3 of the tumors were detected in A-hccM chimeras treated with scrambled ODN. A-hccM were characterized as IL-12-IL-10+CCL1+iNOS-CD14+ cells, while IL-12+IL-10-CCL1-iNOS+CD14+ cells with tumoricidal activities were detected in A-hccM treated with the antisense ODN. These results indicate that M2b monocytes present in A-hccM play a key role in the tumor growth seen in advanced stage hepatocellular carcinoma patients.