High expression levels of IP10/CXCL10 are associated with modulation of the natural killer cell compartment in multiple myeloma

Due to their antimyeloma properties, the interest in the use of NK cells in planning novel immunotherapeutic approaches for this malignancy is recently raised. We have documented that a fraction of multiple myeloma (MM) patients have increased expression levels of the chemokine IP10/CXCL10 in the bone marrow (BM) and blood samples, associated with a marked downmodulation of its receptor, CXCR3, on bone marrow and peripheral blood (PB) NK cells. We compared the frequency of the three NK cell subsets in the BM and PB of a MM patient cohort by immunofluorescence and cytofluorimetric analysis. Our results indicate that the relative ratio of the two subsets (CD56lowCD16low/CD56highCD16+/−) is reduced in the BM of patients with high serum levels of CXCL10 (mean ± SD: MGUS: 2.6 ± 2.6; MM CXCL10low: 2.7 ± 2.1; MM CXCL10high: 1.1 ± 0.8). To investigate whether CXCL10 expression levels define patients with different NK cell functional status, we analyzed the expression of the natural cytotoxicity receptor (NCR) NKp30 and of the activating receptors NKG2D and DNAM-1, in MGUS and MM patients. The expression levels of NKp30 were significantly upregulated in NK cells of BM samples from MM patients with low but not high serum levels of CXCL10 with respect to MGUS patients. The emergence of NKp30 as a targeted receptor in patients displaying high CXCL10 serum levels encourages further investigation, as it may indicate that NK cells functionally interact with myeloma cells through NKp30 or that a series of NKp30-based NK cell evasion strategies are ongoing in this group of patients