1alpha,25-Dihydroxyvitamin D(3) to skew intratumoral levels of immune inhibitory CD34(+) progenitor cells into dendritic cells.

Abstract

Prior studies showed that immune inhibitory CD34(+) progenitor cells, whose numbers are increased in head and neck squamous cell carcinoma (HNSCC) patients, can be differentiated into immune stimulatory dendritic cells by culture with 1alpha,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)). This was extended to a pilot study to diminish intratumoral levels of CD34(+) progenitor cells by inducing their maturation into dendritic cells with 1,25(OH)(2)D(3). Newly diagnosed HNSCC patients were untreated for 3 weeks or received 3 weeks of 1,25(OH)(2)D(3) treatment befoer surgical treatment. HNSCC tissue was collected by biopsy from six patients who had no prior 1,25(OH)(2)D(3) treatment and at the time of surgical treatment from six untreated patients and 11 patients who completed 1,25(OH)(2)D(3) treatment. Tissues were analyzed by immunohistochemistry for levels of CD34(+) cells and dendritic cells. After 1,25(OH)(2)D(3) treatment, intratumoral levels of CD34(+) cells and levels of immature dendritic cells declined. However, levels of intratumoral mature dendritic cells increased. Clinical effects of 1,25(OH)(2)D(3) treatment are premature to analyze. Treatment of HNSCC patients with 1,25(OH)(2)D(3) reduced levels of immune inhibitory CD34(+) cells while increasing maturation of dendritic cells. This supports added studies to determine the effect of 1,25(OH)(2)D(3) on intratumoral immune competence.