Cancer Immunology, Immunotherapy

, Volume 35, Issue 1, pp 14–18 | Cite as

Tumor-derived cytokines induce bone marrow suppressor cells that mediate immunosuppression through transforming growth factor β

  • M. Rita I. Young
  • Mark A. Wright
  • Michael Coogan
  • Melvin E. Young
  • Jamila Bagash
Original articles


Normal bone marrow cells become immunosuppressive when cultured with supernatants of metastatic Lewis lung carcinoma (LLC-LN7) cells. The suppressorinducing activities in the LLC-LN7 supernatants are interleukin-3 and granulocyte/macrophage-colony-stimulating factor. In the present study, the mechanisms by which these induced suppressor cells (LLCsup-BM) mediate their immunosuppression were investigated. The suppression by LLCsup-BM of splenic concanavalin CA blastogenesis was not dependent on cell contact since immunosuppression occurred regardless of whether the LLCsup-BM were separated from the responder spleen cells by a permeable membrane or if the LLCsup-BM were cocultured with the spleen cells. Culture supernatants of LLCsup-BM also inhibited T cell blastogenesis, being more suppressive than were supernatants of control bone marrow cells, which had been precultured with medium. The suppression by the soluble inhibitors elaborated from the LLCsup-BM was not restricted to the inhibition of T cell function as the supernatants also inhibited the natural killer activity of normal spleen cells. Studies to determine the identity of the suppressive activity produced by the LLCsup-BM showed increased levels of transforming growth factor β (TGFβ) in their supernatants. Immunosuppressive bone marrow and spleen cells obtained from mice bearing metastatic LLC-LN7 tumors also secreted more TGFβ than did the cells obtained from normal mice. When anti-TGFβ antibodies were added to the LLCsup-BM supernatants, the suppressive activity was diminished. These results suggest that the LLCsup-BM mediate at least part of their immunosuppression through production of TGFβ.

Key words

Lewis lung carcinoma TGFβ Bone marrow Immunosuppressor 


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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

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

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