Cancer Immunology, Immunotherapy

, Volume 33, Issue 3, pp 146–152

Antibodies to colony-stimulating factors block Lewis lung carcinoma cell stimulation of immune-suppressive bone marrow cells

  • M. Rita I. Young
  • Mark A. Wright
  • Melvin E. Young
Original articles

DOI: 10.1007/BF01756134

Cite this article as:
Young, M.R.I., Wright, M.A. & Young, M.E. Cancer Immunol Immunother (1991) 33: 146. doi:10.1007/BF01756134

Summary

Progressive growth of metastatic Lewis lung carcinoma (LLC) tumors results in a concurrent stimulation of myelopoiesis and the appearance of immune-suppressive bone marrow cells. The present study has shown that normal bone marrow cells could be induced to become immune-suppressive by 3 days of culture with supernatants of cloned metastatic LLC-LN7 variant cells. The capacity of the LLC-LN7 supernatants to stimulate the appearance of suppressor cells was directly proportional to the concentration of supernatant used in the bone marrow culture. When adoptively transferred with a LLC-LN7 tumor inoculum, the supernatant-induced suppressor bone marrow cells increased the rate of appearance of palpable tumors and the frequency of tumor establishment. The LLC-LN7 supernatants containing suppressor-cell-inducing activity also had colony-stimulating factor (CSF) activity. The CSF activity produced by the LLC-LN7 cells could be diminished with neutralizing antibodies to either granulocyte/monocyte(GM-) CSF or to interleukin-3 (IL-3). Likewise, the suppressor-inducing activity in the LLC-LN7 supernatants was diminished by pretreatment with anti-GM-CSF or anti-IL-3. The combination of anti-GM-CSF and anti-IL-3 completely neutralized all suppressor-inducing activity produced by the LLC-LN7 cells. These results suggest that the secretion of IL-3 and GM-CSF by LLC-LN7 tumor cells is a mechanism by which the tumors stimulate myelopoiesis and induce normal bone marrow cells to become immune-suppressive. Bone marrow cells that are induced to become immune-suppressive by culture with LLC-LN7 supernatants can, in turn, facilitate the establishment of tumor in vivo.

Key words

Lewis lung carcinomaGM-CSFIL-3Bone marrowImmune suppressor

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • M. Rita I. Young
    • 1
    • 2
  • Mark A. Wright
    • 1
    • 2
  • Melvin E. Young
    • 1
    • 2
  1. 1.Department of Research ServicesHines V. A. HospitalHinesUSA
  2. 2.Department of PathologyLoyola University Stritch School of MedicineMaywoodUSA