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

Abstract

The mechanism by which hepatocellular carcinoma (HCC) develops and the role of the hepatitis B virus (HBV) in inducing tumors, are not yet well understood. Patients persistently infected with HBV tend to have a defective immune response against the virus, which fails to clear the virus and also induces 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 tumor growth is related to a deviant immune response towards viral or tumor associated antigens. We describe two responses against the tumor. A ‘good’ response that would suppress the tumor and a ‘bad’ response that would promote 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 whether a tumor grows or is suppressed. Oral tolerance involves the induction of immunological hyporesponsiveness towards specific antigens. It was shown that oral tolerance induces antigen-specific immune suppression towards tumor-associated-antigens by feeding of HBV or other tumor proteins. We hypothesize that induction of immune tolerance towards tumor-associated antigens 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 tolerance towards the tumor.