MHC loss in colorectal tumours: evidence for immunoselection?

The reason for MHC loss in colorectal tumours remains uncertain. Strong evidence that the downregulation is due to immunoselective pressure would be provided by the finding of deletions or mutations directly involving MHC heavy chain or beta 2m genes. However, although in contrast to studies on cell lines (Brodsky et al, 1979a; Travers et al, 1986; D'Urso et al, 1991), our findings are in agreement with other evidence (Doyle et al, 1985; Blanchet et al, 1990; Henseling et al, 1990) that the most common mechanism of downregulation is regulatory, mostly at a transcriptional level. Does this imply that MHC loss in tumours can be incidental? The answer to this question will depend on the nature of the initial lesion identified. The existence of cis-acting regulatory mechanisms and dominant negative trans-acting mechanisms suggests that a single mutational event could result in transcriptional changes affecting a number of genes. Thus, selective pressure could result in tumour variants whose loss of MHC is due to transcriptional regulatory changes. As these mechanisms are unravelled, it may be possible to draw conclusions about the aetiology of MHC loss in colorectal tumours. Meanwhile, in the absence of demonstrated CTL to colorectal tumours, the case for immunoselective pressure remains unproven.