Graft versus tumour: suppression of hepatocellular carcinoma growth via induction of oral immune-regulation towards tumour-associated antigens

摘要

Hepatocellular carcinoma (HCC) is associated with persistent hepatitis B virus (HBV) infection. HBV envelope antigen (HBsAg) and/or other HBV proteins expressed on the cell surface may serve as tumour-associated antigens. These epitopes may also serve as targets for the immune system enabling the recognition and destruction of tumour cells. Current treatments for HCC have been disappointing. Chronic immune-mediated liver injury may trigger the development of HCC in the absence of viral transactivation, or insertional mutagene-sis. A defective immune response towards HBV may be involved in the mechanism of HCC6. Attempts to modulate the anti-tumour immunity as a mode of treatment were recently described for various solid and haematological tumours. We have previously shown that adoptive transfer of immunity towards hepatitis B surface antigen (HBsAg) suppressed progression of experimental HBsAg expressing HCC in athymic mice. Oral immune regulation is a mode for immune modulation of a T cell response towards target or bystander antigens. Oral administration of an antigen was shown to decrease or increase epitope-specific immunity in various systems. Tolerance induction is mediated via clonal deletion of antigen-specific T cells, or via an increase in the number of regulatory lymphocytes secreting cytokines suppressing the generation of effector cells. On the other hand, in several models oral immune modulation enhances immunity via secretion of anti-inflammatory or proinflammatory cytokines.