Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3
Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3
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DOI：
10.1007/s00262-003-0459-7
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发表时间：
2004-05-01
影响因子：
5.8
通讯作者：
Young, MRI
中科院分区：
文献类型：
--
作者：
Lathers, DMR;Clark, JI;Young, MRI
头颈部鳞状细胞癌(HNSCC)患者存在严重的免疫缺陷。这些缺陷与不良的预后有关，部分是由免疫抑制的CD34(+)祖细胞介导的，其数量在HNSCC患者的外周血中增加。免疫抑制CD34(+)细胞也存在于HNSCC肿瘤中。对HNSCC患者进行了IB期临床试验，以确定分化诱导剂25-羟基维生素D-3治疗是否可以降低CD34(+)细胞水平并改善一系列免疫参数。在这里，我们介绍了口服递增剂量(20，40，60杯)25-羟基维生素D-3的治疗结果，重点是6名患者，他们每天接受的最大剂量为60杯。分别在0周、1周、2周、4周和6周采集外周血，并对免疫活性标志物进行评估。虽然没有观察到临床反应，但这项初步研究的结果表明，25-羟基维生素D-3治疗HNSCC患者减少了免疫抑制CD34(+)细胞的数量，增加了人类白细胞抗原-DR的表达，增加了血浆IL-12和干扰素-γ的水平，并促进了T细胞的生成。相比之下，25-羟基维生素D-3治疗没有调节血浆IL-1β、IL-2、IL-4、IL-6、IL-10、GM-CSF或转化生长因子-β水平。
Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune defects. These defects are associated with a poor prognosis and are mediated, in part, by immune inhibitory CD34(+) progenitor cells, whose numbers are increased in the peripheral blood of HNSCC patients. Immune inhibitory CD34(+) cells are also present within HNSCC tumors. A phase IB clinical trial was conducted with HNSCC patients to determine if treatment with the differentiation-inducer 25-hydroxyvitamin D-3 could diminish CD34(+) cell levels and improve a panel of immune parameters. Here we present the results of treatment with orally administered escalating doses (20, 40, 60 mug) of 25-hydroxyvitamin D-3, with an emphasis on the six patients who received the maximum dosage of 60 mug per day. Peripheral blood was collected at 0, 1, 2, 4, and 6 weeks, and assessed for markers of immune activity. Although no clinical responses were observed, results of this pilot study demonstrated that treatment of HNSCC patients with 25-hydroxyvitamin D-3 reduces the number of immune suppressive CD34(+) cells, increases HLA-DR expression, increases plasma IL-12 and IFN-gamma levels, and improves T-cell blastogenesis. In contrast, 25-hydroxyvitamin D-3 treatment did not modulate plasma IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, or TGF-beta levels.