Autoregulatory circuits in myeloma: Tumor cell cytotoxicity mediated by soluble CD16

Richard G. Hoover, Cynthia Lary, Robert Page, Patrick Travis, Rebecca Owens, James Flick, Jacki Kornbluth, Bart Barlogie

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Background. Multiple myeloma remains an incurable malignancy due to marked resistance of the tumor to standard doses of chemotherapy. Treatment approaches, using chemotherapeutic dose escalation and hematopoietic stem cell support have resulted in significant augmentation of tumor mass reduction such that complete remissions are effected in ∼50% of patients. These remissions are, however, often not durable. In the setting of minimal residual disease, therefore, adjuctive immunotherapy may be useful. Methods. Peripheral blood mononuclear cells were studied from 28 untreated patients with multiple myeloma (MM). Mononuclear cell CD16 (FcRγ III) expression was determined by flow cytometry. The effect of lymphocyte-derived soluble CD16, isolated by affinity chromatography, on MM cell growth and differentiation was assessed. MM cell proliferation, viability, immunoglobulin production and gene expression was studied. Results. Data are presented indicating that cells expressing CD16 are increased in untreated patients with IgG-secreting myeloma. The predominant phenotype of these cells is CD8+ or CD56+. These CD16+ cells can produce a soluble form of the Fc receptor (sFcR, sCD16) that can bind to surface Ig on cultured human IgG-secreting myeloma cells and effect suppression of tumor cell growth and Ig secretion. This effector function is accompanied by concomitant suppression of c-myc as well as IgH and IgL gene transcription. Finally, prolonged exposure to sCD16 causes myeloma tumor cell cytolysis. Conclusions. sCD16 and possibly other soluble FcR are candidate molecules for adjunctive immunotherapy of myeloma, once complete responses have been effected by intensive cytotoxic therapy, now possible in up to 50% of newly diagnosed patients.

Original languageEnglish
Pages (from-to)241-247
Number of pages7
JournalJournal of Clinical Investigation
Volume95
Issue number1
DOIs
StatePublished - Jan 1995
Externally publishedYes

Keywords

  • CD16
  • Fc receptor
  • Multiple myeloma
  • Suppressor T cell
  • Tumor immunology

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