Skewed differentiation of bone marrow CD34+ cells of tumor bearers from dendritic toward monocytic cells,and the redirection of differentiation toward dendritic cells by 1alpha,25-dihydroxyvitamin D3

Tumor presence is detrimental to the development of antigen-presenting dendritic cells. Since dendritic cells can arise from CD34+ precursor cells, the present study assessed the capacity of bone marrow CD34+ cells from tumor bearers to develop into dendritic cells when cultured in the absence of either tumor cells or their products. Culturing bone marrow CD34+ cells from mice bearing Lewis lung carcinomas yielded a lower number of dendritic cells than arose from CD34+ cells of normal mice. This reduced yield of dendritic cells was associated with a shift to development of monocytic cells and a reduced antigen presenting capability by the cultures. When the CD34+ cell cultures from tumor bearers were supplemented with the differentiation-inducing hormone 1alpha,25-dihydroxyvitamin D3, there was the restoration of dendritic cell development and antigen presenting ability. These results show that CD34+ cells from tumor bearers remain defective in their development into dendritic cells even when cultured outside the tumor environment, but development of dendritic cells can be restored with 1alpha,25-dihydroxyvitamin D3.