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Cancer Immunology, Immunotherapy

, Volume 41, Issue 1, pp 37–45 | Cite as

Treating tumor-bearing mice with vitamin D3 diminishes tumor-induced myelopoiesis and associated immunosuppression, and reduces tumor metastasis and recurrence

  • M. Rita I. Young
  • Joe Ihm
  • Yvonne Lozano
  • Mark A. Wright
  • M. Margaret Prechel
Original Article Tumor, Immunosuppressor cells, Myelopolesis, GM-CSF, Metastasis, Vitamin D3

Abstract

Metastatic Lewis lung carcinoma (LLC-LN7) tumors that secrete granulocyte/macrophage-colonystimulating factor (GM-CSF) stimulate myelopoiesis and induce bone marrow-derived immunosuppressor cells that are homologous to granulocyte/macrophage progenitor cells. In vitro treatment of the LLC-LN7 cells with 1α,25-dihydroxyvitamin D3 reduced tumor cell production of suppressor-inducing activity, although suppressor-inducing activity could be restored by reconstituting the tumor supernatants with recombinant GM-CSF. Treatment of mice having LLC-LN7 tumors with vitamin D3 reduced tumor production of GM-CSF and the frequency of myeloid progenitor cells. This was associated with a reduction in immunosuppressor activity and an increase in T cell function. Vitamin D3 treatment of mice having palpable tumors transiently retarded tumor growth, but caused a prominent reduction in tumor metastasis. Treating mice with vitamin D3 after tumor excision resulted in a reduction in the tumor-induced myelopoietic stimulation and associated immunosuppressive activity, and enhanced T cell function. These mice had a markedly reduced incidence of tumor recurrence. The results of this study suggest that vitamin D3 treatment of mice with GM-CSF-secreting tumors can interrupt the myelopoiesis-associated immunosuppressor cascade and, in turn, reduce tumor metastasis and recurrence.

Key words

Tumor Immunosuppressor cells Myelopoiesis GM-CSF Metastasis Vitamin D3 

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • M. Rita I. Young
    • 1
    • 2
  • Joe Ihm
    • 1
  • Yvonne Lozano
    • 1
  • Mark A. Wright
    • 1
  • M. Margaret Prechel
    • 2
  1. 1.Research Service (151-Z2), Department of Veterans AffairsHines VA HospitalHinesUSA
  2. 2.Departments of Pathology and OtolaryngologyLoyola University Stritch School of MedicineMaywoodUSA

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