1α,25-Dihydroxyvitamin D3 to skew intratumoral levels of immune inhibitory CD34+ progenitor cells into dendritic cells

OBJECTIVES: 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 1 alpha,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. STUDY DESIGN: Newly diagnosed HNSCC patients were untreated for 3 weeks or received 3 weeks of 1,25(OH)(2)D-3 treatment befoer surgical treatment. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.