The demonstration that for infectious diseases vaccine-induced immunity is in principle only effective before rather than after infection occurs,provides valuable insights in understanding the nature of immune system and the challenges in cancer treatment.Besides the already known underlying counter-back mechanisms,the astronomical numbers of tumor cells in established tumors could overwhelm the limited amount of specific T cells induced by vaccination,which may account for the modest efficiency of immunotherapy against cancer.We speculate that the long window period for cancer development will allow immune-intervening strategies(e.g.,the proper prophylactic vaccination)to promote adaptive mechanisms toward an enhanced immunosurveillance,which could effectively eradicate or at least control the few precancerous cells undergoing neoplastic transformation during early premalignant stages in cancer development,and protect the host from lethal tumor formation.It should be emphasized that the pre-cancer-associated antigens but not the tumorassociated antigens seem to be the suitable antigens for designing prophylactic cancer vaccines.In addition,an ideal prophylactic cancer vaccine may contain multiple pre-cancer-associated antigens,which will provide broad and effective immune protection in a heterogeneous human population.Finally,we demonstrated that placenta-derived gp96,which can be readily obtained in high amount for vaccination,has the ability to initiate antitumor T-cell immunity via association with multiple embryo-cancer antigens.Further understanding placental gp96 associated with carcinoembryonic antigen repertoires that orchestrate immune defense networks against cancer formation will allow to provide an effective prophylactic approach in cancer prevention.
As the most abundant liver-specific microRNA,mi-croRNA-122(miR-122)is involved in various physio-logical processes in hepatic function as well as in liver pathology.There is now compelling evidence that miR-122,as a regulator of gene networks and pathways in hepatocytes,plays a central role in diverse aspects of hepatic function and in the progress of liver diseases.This liver-enriched transcription factors-regulated miRNA promotes differentiation of hepatocytes and regulates lipid metabolism.With regard to liver diseases,miR-122 was shown to stimulate hepatitis C virus(HCV)replication through a unique and unusual interaction with two binding sites in the 5′-UTR of HCV genome to mediate the stability of the viral RNA,whereas inhibit the expression and replication of hepatitis B virus(HBV)by a miR-122-cylin G1/p53-HBV enhancer regulatory pathway.In addition,miR-122 acts as a suppressor of cell prolif-eration and malignant transformation of hepatocytes with remarkable tumor inhibition activity.Notably,a clinical trial targeting miR-122 with the anti-miR-122 oli-gonucleotides miravirsen,the first miRNA targeted drug,has been initiated for treatment of HCV infection.With further understanding of the comprehensive roles of miR-122 in hepatic functions and the mechanisms in-volved in miR-122 down-regulation in chronic hepatitis or hepatocellular carcinoma,miR-122 appears to be a promising candidate for effective therapeutic ap-proaches against tumor and infectious diseases.
Jun HuYaxing XuJunli HaoSaifeng WangChangfei LiSongdong Meng
