HLA Antigen Expression and Malignant Mesothelioma

The expression of HLA antigens by a tumor may determine its progression and metastic potential by influencing the immune response to that tumor. The upregulation of HLA antigen expression on some cell types by interferons (IFNs) may contribute to their antitumor activity. Malignant mesothelioma (MM) is a tumor that has a poor prognosis and is unaffected by conventional therapy, although immunotherapy has not been adequately assessed. In this study, we have examined the constitutive and IFN-inducible expression of class I and class II HLA antigens on MM cell lines using indirect immunofluorescence and Northern blotting. All MM cell lines constitutively expressed class I, but not class II, surface antigen, and all three class I loci (HLA-A, HLA-B, and HLA-C) were expressed. The MM cell lines were heterogeneous in their response to the IFNs. Treatment with IFN-α marginally increased class I surface expression, but not class II. Class I mRNA was, however, clearly increased in all cell lines after IFN-α treatment, suggesting that class I surface antigen was already maximally expressed. IFN-γ increased class I mRNA expression in all but one cell line and induced DR expression on three of the cell lines. DQ-β, but not DQ-α, mRNA was inducible in the same three cell lines, but DQ surface antigen was never demonstrable. The defects in DR and DQ expression were heterogeneous, occurring either at the level of transcription or at the level of the IFN-γ receptor in different cell lines. The growth of four out of the five cell lines was inhibited by both IFNs. IFN-α and IFN-γ treatment resulted in minimal decreases in lymphokine-activated killer cell sensitivity in all cell lines, and the already low natural killer cell susceptibility was unaffected. IFN-α and IFN-γ may contribute to the control of growth of MM in some cases by enhancing specific antitumor responses via induction of major histocompatibility complex antigen expression and via direct antiproliferative effects without compromising nonspecific cytotoxic mechanisms.