Kulbersh Jonathan S, Day Terry A, Gillespie M Boyd, Young M Rita I
Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA.
Otolaryngol Head Neck Surg. 2009 Feb;140(2):235-40. doi: 10.1016/j.otohns.2008.11.011.
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) (1,25OHD(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.
先前的研究表明,免疫抑制性CD34(+)祖细胞在头颈部鳞状细胞癌(HNSCC)患者中数量增加,通过与1α,25-二羟基维生素D(3)(1,25OHD(3))培养可分化为免疫刺激性树突状细胞。本研究扩展为一项初步研究,通过用1,25(OH)(2)D(3)诱导其成熟为树突状细胞来降低肿瘤内CD34(+)祖细胞水平。
新诊断的HNSCC患者未经治疗3周或在手术治疗前接受3周的1,25(OH)(2)D(3)治疗。
通过活检从6例未接受过1,25(OH)(2)D(3)治疗的患者中收集HNSCC组织,并在手术治疗时从6例未治疗患者和11例完成1,25(OH)(2)D(3)治疗的患者中收集。通过免疫组织化学分析组织中CD34(+)细胞和树突状细胞的水平。
1,25(OH)(2)D(3)治疗后,肿瘤内CD34(+)细胞水平和未成熟树突状细胞水平下降。然而,肿瘤内成熟树突状细胞水平增加。1,25(OH)(2)D(≥)治疗的临床效果尚早,无法分析。
用1,25(OH)(2)D(3)治疗HNSCC患者可降低免疫抑制性CD34(+)细胞水平,同时增加树突状细胞的成熟度。这支持进一步研究以确定1,25(OH)(2)D(3)对肿瘤内免疫能力的影响。