Cancer Immunology, Immunotherapy

, Volume 46, Issue 5, pp 253–260

Stimulation of immune suppressive CD34+ cells from normal bone marrow by Lewis lung carcinoma tumors

  • Mark A. Wright
  • Kristina Wiers
  • Kishore Vellody
  • Dragana Djordjevic
  • M. Rita I. Young
ORIGINAL ARTICLE

DOI: 10.1007/s002620050485

Cite this article as:
Wright, M., Wiers, K., Vellody, K. et al. Cancer Immunol Immunother (1998) 46: 253. doi:10.1007/s002620050485

Abstract

 Progressive growth of metastatic Lewis lung carcinoma (LLC-LN7) tumors is associated with increased levels of bone-marrow-derived CD34+ cells having natural suppressor (NS) activity toward T cells. The present studies determined whether tumor-derived products are responsible for this induction of NS activity. Culturing normal bone marrow cells with LLC-LN7-conditioned medium (LLC-CM) or with recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) resulted in the appearance of NS activity. The development of NS activity coincided with a prominent increase in the levels of CD34+ cells. That the CD34+ cells were responsible for the NS activity of the bone marrow cultures containing LLC-CM was shown by the loss of NS activity when CD34+ cells were depleted. The stimulation of CD34+ NS cells by LLC-CM was attributed to tumor production of GM-CSF, since neutralization of GM-CSF within the LLC-CM reduced its capacity to increase CD34+ cell levels. Studies also showed that the induction of CD34+ NS cells by LLC-CM and GM-CSF could be overcome by including in the cultures an inducer of myeloid differentiation, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. These results demonstrate that the mechanism by which the LLC-LN7 tumors stimulate increased levels of CD34+ NS cells from normal bone marrow is by their production of GM-CSF and that this can be blocked with the myeloid differentiation inducer 1,25(OH)2D3.

Key words Natural suppressor cellsImmune suppressor cellsCD34+ cellsTumorCancer

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Mark A. Wright
    • 1
  • Kristina Wiers
    • 2
  • Kishore Vellody
    • 1
  • Dragana Djordjevic
    • 1
  • M. Rita I. Young
    • 1
  1. 1.Research Service (151-Z2), Hines VA Hospital, Hines, IL 60141, USA Tel. +1 708 343 7200 ext. 5749; Fax +1 708 216 2319 e-mail: myoung1@luc.eduUS
  2. 2.Departments of Pathology and Otolaryngology, Loyola University Stritch School of Medicine, Maywood, IL 60153, USAUS