Differential expression of natural killer cell activating receptors in blood versus bone marrow in patients with monoclonal gammopathy

Immunology. 2013 Jul;139(3):338-41. doi: 10.1111/imm.12082.

Abstract

In monoclonal gammopathies (MG) and multiple myeloma (MM), normal natural cytotoxicity receptors (NCR) expression (NCR1/NKp46, NCR2/NKp44, NCR3/NKp30) is observed in natural killer (NK) cells. Nonetheless, except in plasma cell leukemia, few tumor plasmocytes are present in PB, while NK studies have been performed on peripheral blood (PB). For this reason we focused our attention on NK from bone marrow (BM). Our study demonstrates that the down-regulation of NCR3/NKp30 is only detectable in NK from BM but not in PB, and shows a drastic decrease of both NKG2D and CD244/2B4/p38 expression in NK from BM in comparison with PB. In conclusion, our data more precisely describe the mechanism of immune escape of MG/MM from innate immunity since we show a drastic down regulation of 3 major activating NK receptors (NCR3/NKp30, NKG2D and CD244/2B4/p38) at the site of tumor, i.e BM, that was undetectable in PB. Further studies regarding immune regulatory drugs in MG/MM will imperiously require the assessment of immune cell status not only in PB but also in BM to obtain more relevant data regarding anti-tumor efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / metabolism
  • Bone Marrow / immunology
  • Bone Marrow / metabolism*
  • Down-Regulation*
  • Female
  • Humans
  • Killer Cells, Natural / immunology*
  • Male
  • Middle Aged
  • Multiple Myeloma / genetics
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / metabolism
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Natural Cytotoxicity Triggering Receptor 3 / metabolism
  • Paraproteinemias / genetics
  • Paraproteinemias / immunology*
  • Paraproteinemias / metabolism
  • Receptors, Immunologic / metabolism
  • Receptors, Natural Killer Cell / blood
  • Receptors, Natural Killer Cell / immunology
  • Receptors, Natural Killer Cell / metabolism*
  • Signaling Lymphocytic Activation Molecule Family

Substances

  • Antigens, CD
  • CD244 protein, human
  • KLRK1 protein, human
  • NCR3 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 3
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Signaling Lymphocytic Activation Molecule Family