Downmodulation of MHC

A number of small-scale assessments of MHC class I expression and its loss by metastatic melanomas have been conducted using IHC staining, indicating that loss of class I expression confers a worse prognosis.129-134 The majority of melanomas show normal staining for the nonpolymorphous class I A, B, C determinants, without evidence for allele-spe-cific deletion or downregulation. Less than 10% of tumors show deletion of the beta-2 microglobulin gene, resulting in complete loss of class I expression. Approximately 10% to 40% of tumors demonstrate a decrease in class I staining or with antibody MA 2.1 recognizing class I allele A2 due to downregulation of mRNA expression or gene deletion causing absent expression of that allele. Fourteen primary melanomas were examined in one study, with MHC allele loss seen by IHC in 20%.131 In a study of 48 metastatic lesions from 39 patients, loss of HLA class I expression of more than 50% was seen and was associated with a poorer clinical outcome.132 Loss of HLA class I diminished immune recognition by melanoma-specific T cells in vitro,134 although the effects on immune response to a vaccine are unclear.

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