Phase IB study of 25-hydroxyvitamin D(3) treatment to diminish suppressor cells in head and neck cancer patients.
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 an increased number of immune inhibitory CD34(+) progenitor cells in their peripheral blood and tumor. The CD34(+) cells suppress autologous T-cell functions. Our prior work had shown that the differentiation inducer 1alpha,25-dihydroxyvitamin D(3) could drive the differentiation of CD34(+) cells isolated from HNSCC patients into dendritic cells. A phase IB clinical trial was initiated with HNSCC patients to determine if 25-hydroxyvitamin D(3) treatment could diminish CD34(+) cell levels and improve immune function. Six patients per treatment group were orally administered 20 or 40 microg/day 25-hydroxyvitamin D(3) for six weeks. Peripheral blood was collected at 0, 1, 2, 4, 6, and 8 weeks, and assessed for markers of immune activity. Although no clinical responses were observed, results of these pilot studies showed that 25-hydroxyvitamin D(3) reduced the presence of immune suppressive CD34(+) cells and improved immune competence of HNSCC patients.
Lathers
D M
DM
Research Service, Hines Veterans Affairs Hospital, Hines, Illinois 60141, USA. dlather@luc.edu
Clark
J I
JI
Achille
N J
NJ
Young
M R
MR
D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D002112:Calcifediol / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000097:blood; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
D018952:Antigens, CD34; D006684:HLA-DR Antigens; D018664:Interleukin-12; D002112:Calcifediol