Tumor-primed natural killer cells from patients with multiple myeloma lyse autologous, NK-resistant, bone marrow-derived malignant plasma cells

✍ Scribed by Eirini Katodritou; Evangelos Terpos; Janet North; Panagiotis Kottaridis; Evgenia Verrou; Vasiliki Gastari; Christina Chadjiaggelidou; Shivajanani Sivakumaran; Samuel Jide-Banwo; Maria Tsirogianni; Dimitrios Kapetanos; Konstantinos Zervas; Mark W. Lowdell

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 716 KB
• Volume: 86
• Category: Article
• ISSN: 0361-8609
• DOI: 10.1002/ajh.22163

✦ Synopsis

Abstract

Natural killer (NK) cells are cytotoxic lymphocytes able to kill tumor cells and virus‐infected cells. Human‐resting NK cells can be activated by co‐culture with NK‐resistant CTV‐1a cells. These tumor‐activated cells (TaNKs) are cytotoxic to a range of NK‐resistant tumor cells in vitro. This potential, however, has not been explored in multiple myeloma (MM). In this study, we demonstrate that TaNK cells from 21 MM patients lyse a variety of myeloma targets, including primary isolates of autologous and allogeneic CD138+ myeloma cells whilst sparing CD138−ve bone marrow cells. Myeloma patients' TaNK‐induced lysis of the U266 cell line was significantly higher compared to normal controls (median‐specific lysis 79.1% vs. 69.5%) (P = 0.003). In addition, TaNKs induced substantial lysis of autologous and allogeneic CD138+ myeloma cells (median‐specific lysis 52.5% and 37.4%, respectively). The percentage of specific lysis did not correlate with important disease characteristics (ISS, age, and high‐risk molecular abnormalities) or with the disease status and antimyeloma treatment, including novel agents and dexamethasone. In conclusion, tumor‐primed NK cells are able to induce substantial lysis of myeloma targets including autologous and allogeneic CD138+ myeloma plasma cells and could be an additional therapeutic approach in MM, particularly in the era of novel agents. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.