Changes in MHC Class I expression, MICA/B and CD95 during the progression of MGUS to Multiple Myeloma: evidence of a NK-mediated cell immunoedition

摘要

The molecular basis of MGUS progression to a malignant monoclonal gammopathy remains poorly understood. It was recently suggested that this process involves the suppression of innate and adaptive immunity. In this study, we examined immunogenic differences in bone marrow plasma cells among: individuals without gam-mopathy (controls) and patients with MGUS, Multiple Myeloma (MM) and Plasma Cell Leukaemia (PCL). We detected differences in MHC class I expression, MICA and CD95 that were more evident between MGUS and MM samples; there appeared to be a critical imbalance between NK cell activating and inhibitory signals during the transition from MGUS to MM. Our results indicate that the HLA class I~(bright), MICA~(dim/-) and CD95~(dim/-) immunophenotype found in myeloma cells may result from an extensive interaction of malignant cells with cytotoxic T and NK cells and appears to be immunoedited for evading immunosurveillance.