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

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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.

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Authors and Affiliations

  1. Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA

    M. Rita I. Young, Mark A. Wright & Melvin E. Young

  2. Department of Pathology, Loyola University Stritch School of Medicine, 60 153, Maywood, IL, USA

    M. Rita I. Young, Mark A. Wright & Melvin E. Young

Authors
  1. M. Rita I. Young
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  2. Mark A. Wright
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  3. Melvin E. Young
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Additional information

This study was supported by the Medical Research Services of the Veterans Administration and by grant CA-45080 from the National Institutes of Health

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Young, M.R.I., Wright, M.A. & Young, M.E. Antibodies to colony-stimulating factors block Lewis lung carcinoma cell stimulation of immune-suppressive bone marrow cells. Cancer Immunol Immunother 33, 146–152 (1991). https://doi.org/10.1007/BF01756134

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  • DOI: https://doi.org/10.1007/BF01756134

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