Mutations of the beta(2)-microglobulin gene result in a lack of HLA class I molecules on melanoma cells of two patients immunized with MAGE peptides

Mutations have been identified in the beta(2)-microglobulin gene of tumor c ells of two metastatic melanoma patients who received immunizations with MA GE peptides, One mutation abolishes the start codon whereas the other intro duces a premature stop codon, The second beta(2)-microglobulin allele of bo th tumors appears to be lost on the basis of sequence data and loss of micr osatellite heterozygosity. The lack of beta(2)-microglobulin gene product r esults in the absence of HLA class I antigens on the surface of the tumor c ells. This may explain why the tumors of both patients progressed despite t he immunization treatment and shows the necessity of analyzing in depth the antigen presentation capability of the tumor cells for the interpretation of clinical trials involving anti-tumor vaccination.