The biological consequences of altered MHC expression on tumours.

Abstract

The biological importance of MHC molecules in host tumour interactions is reviewed. It is clear from both experimental and clinical investigations that there are important consequences of both the quantitative and qualitative variations in the expression of MHC antigens. The selective absence of certain detectable syngeneic class I antigens significantly affects the host immune response to tumour associated transplantation antigens in the Gross virus experimental model. This is believed to be due to MHC restricted responses. There is a clear quantitative relationship between the amount of the relevant class I restriction element present on these tumours and the host immune response to the tumour as detected by in vitro cytotoxicity and cytostasis tests and also in in vivo tumour progression. The host response to the tumour can be radically altered by causing the re-expression of the relevant class I restriction element following gene transfection. The quantitative balance between the antigens of the two class I loci is also important in determining the frequency of metastasis. The molecular basis of the expression of novel MHC allo-antigen like molecules on syngeneic tumours is now better understood and is believed to arise from gene conversion or rearrangement possibly involving multiple silent Qa and Tla a-like genes and MHC pseudogenes and following insults by toxic chemicals, radiation effects and viruses. The biological effects of these antigens is still being investigated and may involve both tumour surveillance or tumour promotion depending on the nature of the novel molecule expressed.