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

  • Original Article
  • Tumor, Immunosuppressor cells, Myelopolesis, GM-CSF, Metastasis, Vitamin D3
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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.

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Authors and Affiliations

  1. Research Service (151-Z2), Department of Veterans Affairs, Hines VA Hospital, 60141, Hines, IL, USA

    M. Rita I. Young, Joe Ihm, Yvonne Lozano & Mark A. Wright

  2. Departments of Pathology and Otolaryngology, Loyola University Stritch School of Medicine, 60153, Maywood, IL, USA

    M. Rita I. Young & M. Margaret Prechel

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  1. M. Rita I. Young
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  2. Joe Ihm
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  3. Yvonne Lozano
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  4. Mark A. Wright
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  5. M. Margaret Prechel
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This study was supported in part by grants from the Medical Research Service of the Department of Veterans Affairs and by grants CA-45080 and CA-48080 from the National Institutes of Health

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Young, M.R.I., Ihm, J., Lozano, Y. et al. Treating tumor-bearing mice with vitamin D3 diminishes tumor-induced myelopoiesis and associated immunosuppression, and reduces tumor metastasis and recurrence. Cancer Immunol Immunother 41, 37–45 (1995). https://doi.org/10.1007/BF01788958

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  • DOI: https://doi.org/10.1007/BF01788958

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