title: Tumor-primed natural killer cells from patients with multiple myeloma lyse autologous, NK-resistant, bone marrow-derived malignant plasma cells.
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.
authors.affiliation: Department of Hematology, University College Medical School, London, United Kingdom. eirinikatodritou@gmail.com
authors.forename: Eirini
authors.initials: E
authors.lastname: Katodritou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Janet
authors.initials: J
authors.lastname: North
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kottaridis
authors.forename: Evgenia
authors.initials: E
authors.lastname: Verrou
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Gastari
authors.forename: Christina
authors.initials: C
authors.lastname: Chadjiaggelidou
authors.forename: Shivajanani
authors.initials: S
authors.lastname: Sivakumaran
authors.forename: Samuel
authors.initials: S
authors.lastname: Jide-Banwo
authors.forename: Maria
authors.initials: M
authors.lastname: Tsirogianni
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kapetanos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zervas
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lowdell
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D053668:Syndecan-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; C508241:SDC1 protein, human; D053668:Syndecan-1; D003907:Dexamethasone