Cancer: a biological problem without any natural immunological solution? A unified theory, with implications for...

Stem tumour cells would be paraembryonal cells, major histocompatibility complex lacking and able of inducing adjoining cells to become tumour differentiated cells with major histocompatibility complex; thus, they would generate a histological tumour organization into paraembryonal cell clusters surrounded by tumour-differentiated cells. Such an organization, actually found in recent studies, might be one factor responsible for the limits of the immunotherapies carried out so far. But, there might be another, perhaps more important, factor. Analysis of ontogenetic aspects of MHC-nonrestricted immunity would lead, indeed, to the prediction that natural killer clones reactive for stem tumour cells (paraembryonal cells) would be missing in the adult organism, since they would be deleted in particular ontogenetic phases. This might explain why natural killer cells locate only in certain organs and nearly not at all in tumour sites. By such an analysis, possible evolutive and functional correlations between natural killer cells and heat shock proteins, hemopoietic histocompatibility, major histocompatibility complex molecules are suggested. From here, explanations and implications for grafts, pregnancy and tumour immunoprophylaxis arise.