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

Abstract

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 1α,25-dihydroxyvitamin D₃ (1,25[OH]₂D₃). 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)₂D₃.

Study Design: Newly diagnosed HNSCC patients were untreated for 3 weeks or received 3 weeks of 1,25(OH)₂D₃ treatment befoer surgical treatment.

Subjects and Methods: HNSCC tissue was collected by biopsy from six patients who had no prior 1,25(OH)₂D₃ treatment and at the time of surgical treatment from six untreated patients and 11 patients who completed 1,25(OH)₂D₃ treatment. Tissues were analyzed by immunohistochemistry for levels of CD34⁺ cells and dendritic cells.

Results: After 1,25(OH)₂D₃ 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)₂D₃ treatment are premature to analyze.

Conclusions: Treatment of HNSCC patients with 1,25(OH)₂D₃ 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)₂D₃ on intratumoral immune competence.