Treating tumor-bearing mice with vitamin D3 diminishes tumor-induced myelopoiesis and associated immunosuppression, and reduces tumor metastasis and recurrence.
Metastatic Lewis lung carcinoma (LLC-LN7) tumors that secrete granulocyte/macrophage-colony-stimulating 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 1 alpha,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.
Young
M R
MR
Research Service (151-Z2), Department of Veterans Affairs, Hines VA Hospital, IL 60141, USA.
Ihm
J
J
Lozano
Y
Y
Wright
M A
MA
Prechel
M M
MM
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D002762:Cholecalciferol / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006410:Hematopoiesis / Q000187:drug effects*; D007111:Immunity, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
D002762:Cholecalciferol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor