GRA15Ⅱ Against Hepatic Carcinoma in Mice via Promotion of Macrophage Polarization in Tumor Microenvironment
Tumor-associated macrophages(TAMs)play an important role in the development of tumors.The aim of the present study was to investigate the role of the dense granule protein molecule of Toxoplasma gondii(GRA15Ⅱ)in inhibition of the tumor growth via macrophage polarization.Here,we constructed a recombinant LV-GRA15n and injected it into tumor bearing C57BL/6 mice for analyzing the immune responses in tumor microenvironment by RT-PCR,ELISA,IHC,FCM and LSCM.GRA15Ⅱ induced the repolarization of M2-like macrophages without affecting the M1 phenotype in vitro.Additionally,GRA15Ⅱ inhibited the tumor growth and induced the TAM polarization from M2-like to M1-like by TRAF6-NF-κB pathway activation.Furthmore,expression of NO,IL-12 and TNF-α was upregulated to enhance Th1 immune response in the tumor microenvironment.In conclusion,GRA15Ⅱ inhibited the tumor growth,which might lead to new immunotherapy strategies and experimental research for the development of new drugs to tumor treatment.