TREATING TUMOR-BEARING MICE WITH VITAMIN-D-3 DIMINISHES TUMOR-INDUCEDMYELOPOIESIS AND ASSOCIATED IMMUNOSUPPRESSION, AND REDUCES TUMOR-METASTASIS AND RECURRENCE

Metastatic Lewis lung carcinoma (LLC-LN7) tumors that secrete granuloc yte macrophage-colony-stimulating factor (GM-CSF) stimulate myelopoies is and induce bone marrow-derived immunosuppressor cells that are homo logous to granulocyte macrophage progenitor cells. In vitro treatment of the LLC-LN7 cells with 1 alpha 25-dihydroxyvitamin D-3 reduced tumo r cell production of suppressor-inducing activity, although suppressor -inducing activity could be restored by reconstituting the tumor super natants with recombinant GM-CSF. Treatment of mice having LLC-LN7 tumo rs with vitamin D-3 reduced tumor production of GM-CSF and the frequen cy of myeloid progenitor cells. This was associated with a reduction i n immunosuppressor activity and an increase in T cell function. Vitami n D-3 treatment of mice having palpable tumors transiently retarded tu mor growth but caused a prominent reduction in tumor metastasis. Treat ing mice with vitamin D-3 after tumor excision resulted in a reduction in the tumor-induced myelopoietic stimulation and associated immunosu ppressive activity, and enhanced T cell function. These mice had a mar kedly reduced incidence of tumor recurrence. The results of this study suggest that vitamin D-3 treatment of mice with GM-CSF-secreting tumo rs can interrupt the myelopoiesis-associated immunosuppressor cascade and in turn reduce tumor metastasis and recurrence.