High Frequency of Allele-specific Down-regulation of HLA class I Expression in Lung Cancer Cell Lines

Loss or down-regulation of HLA expression has been demonstrated in various types of solid tumors and is considered to be one of the mechanisms of tumor immunoescape. The effectiveness of immunotherapy using tumor-specific antigens (TSA) largely depends on the expression of the appropriate HLA class I alleles on the tumor cells. We analyzed the allele-specific HLA class I surface expression of six lung cancer cell lines using a broad panel of allele-specific monoclonal antibodies, as well as the effect of IFN-A on HLA expression. Flow cytometric analysis displayed a wide range, from minimal to a high degree of expression of monomorphic HLA class I among the studied cell lines. Allele- specific loss or down-regulation of HLA also was observed in 5 out of 6 cell lines. Our results suggest that lung cancer patients considered for specific immunotherapy should be examined with respect to the expression of specific HLA class I allele binding the TSA. Lung cancer is the leading cause of cancer death in most industrialized countries and it has a poor prognosis. Despite recent progress in chemotherapy and molecular-targeted drugs against advanced lung cancers, these therapies have little impact on survival and the majority of patients with advanced lung cancer die within a few years (1). Therefore, new therapeutic modalities including immunotherapy using tumor-specific antigen (TSA) or cytotoxic T lymphocytes (CTL) should be urgently advanced. During the past decade, a large number of TSA recognized by CTL were identified (2), some of them being expressed in lung cancer. These antigens opened up new possibilities for the immunotherapy of lung cancer and several vaccination trials are now underway aimed at inducing a strong CTL response against defined TSA. Since TSA are most often intracellular proteins expressed in association with the membrane-bound human leukocyte antigen (HLA) class I molecules, whether