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

Am J Hematol. 2011 Dec;86(12):967-73. doi: 10.1002/ajh.22163. Epub 2011 Sep 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Bone Marrow / drug effects
  • Bone Marrow / pathology
  • Cell Line, Tumor
  • Coculture Techniques
  • Cytotoxicity, Immunologic* / drug effects
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Disease Progression
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / drug effects
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / immunology
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Plasma Cells / drug effects
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Plasma Cells / pathology*
  • Syndecan-1 / metabolism
  • Tumor Cells, Cultured

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • SDC1 protein, human
  • Syndecan-1
  • Dexamethasone