Soluble MICA as an independent prognostic factor for the overall survival and progression-free survival of multiple myeloma patients

Major histocompatibility complex class I-related chain A (MICA) molecules are frequently expressed in lymphoproliferative malignancies including multiple myeloma (MM). MICA activates NK cells and co-stimulates T cells by interaction with its immunoreceptor NKG2D. In contrast, soluble MICA (sMICA) molecules impair the functions of NKG2D+ T and NK cells, which may facilitate tumor cell escape from immunosurveillance. Here, we analyzed the clinical relevance of sMICA in 97 MM patients. sMICA (mean ± SEM pg/ml) was significantly increased (p < 0.0001) in patients (429 ± 20) compared to controls (230 ± 20; N = 43). Serial determination showed a strong correlation between increments of sMICA and paraprotein levels (r = 0.543, p < 0.0001, N = 49). sMICA levels > 305 pg/ml are associated with a poor overall (p = 0.004) and progression-free survival (p = 0.002). Multivariate analysis revealed sMICA as an independent predictive factor for overall (p = 0.007) and progression-free survival (p = 0.002). Thus, our results suggest sMICA as a potent prognostic marker in MM, which may be useful to identify risk patients.