LOSS OF TRANSPORTER PROTEIN, ENCODED BY THE TAP-1 GENE, IS HIGHLY CORRELATED WITH LOSS OF HLA EXPRESSION IN CERVICAL CARCINOMAS

Malignant tumor cells can escape CD8(+) cytotoxic T cell killing by do wnregulating class I major histocompatibility complex (MHC) expression . Stable class I MHC surface expression requires loading of the heavy chain/light chain dimer with antigenic peptide, which is delivered to class I MHC molecules in the endoplasmic reticulum by the presumed pep tide transporter, encoded by the transporter associated with antigen p resentation (TAP) 1 and 2 genes. We have investigated whether loss of class I MHC expression frequently observed in different cancers could result from interference with TAP function. A polyclonal antiserum, ra ised against a bacterial glutathione S-transferase/human TAP-1 fusion protein, was used for the immunohistochemical analysis of TAP-1 expres sion in 76 cervical carcinomas. Results showed loss of TAP-1 expressio n in neoplastic cells in 37 out of 76 carcinomas. Immunohistochemical double staining procedures in combination with HLA-specific antibodies revealed congruent loss at the single cell level of TAP-1 and HLA-A/B expression in 28 out of 37 carcinomas. The remaining samples expresse d HLA(-A) in the absence of TAP-1 (n = 6) or showed loss of HLA(-A/B) while TAP-1 was expressed (n = 3). These data strongly indicate that i nhibition of peptide transport by downregulation of TAP-1 is a potenti al strategy of malignant cells to evade immune surveillance.