Downregulation of a tumor promotion immune response via induction of oral tolerance towards tumor- associated-antigens: can we 'eat the tumor?

The mechanism by which hepatocellular carcinoma (HCC) develops and the role of the hepatitis B virus (HBV) in inducing tumors, are not yet well unders tood. Patients persistently infected with HBV tend to have a defective immu ne response against the virus, which fails to dear the virus and also induc es liver injury. This defective response may also have an inducible effect on the virus and on cells that express HBV antigens, as well as play a role in the growth of neoplasm. It is possible that one of the mechanisms of tu mor growth is related to a deviant immune response towards viral or tumor a ssociated antigens. We describe two responses against the tumor. A 'good' r esponse that would suppress the tumor and a 'bad' response that would promo te it and theorize that the net balance between 'bad' and 'good' responses of the immune system towards a cancerous cell and/or antigen will predict w hether a tumor grows or is suppressed. Oral tolerance involves the inductio n of immunological hyporesponsiveness towards specific antigens, It was sho wn that oral tolerance induces antigen-specific immune suppression towards tumor-associated-antigens by feeding of HBV or other tumor proteins. We hyp othesize that induction of immune tolerance towards tumor-associated antige ns will suppress the immune response towards these antigens, thus reducing the 'bad' response. The proposed new treatment strategy would redirect the focus from augmenting anti-tumor immune responses to inducing host toleranc e towards the tumor. (C) 2001 Harcourt Publishers Ltd.