Cancer Immunology, Immunotherapy

, Volume 53, Issue 5, pp 422–430

Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3

  • Deanne M. R. Lathers
  • Joseph I. Clark
  • Nicholas J. Achille
  • M. Rita I. Young
Original Article

DOI: 10.1007/s00262-003-0459-7

Cite this article as:
Lathers, D.M.R., Clark, J.I., Achille, N.J. et al. Cancer Immunol Immunother (2004) 53: 422. doi:10.1007/s00262-003-0459-7
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Abstract

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 D3 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 μg) of 25-hydroxyvitamin D3, with an emphasis on the six patients who received the maximum dosage of 60 μg 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 D3 reduces the number of immune suppressive CD34+ cells, increases HLA-DR expression, increases plasma IL-12 and IFN-γ levels, and improves T-cell blastogenesis. In contrast, 25-hydroxyvitamin D3 treatment did not modulate plasma IL-1β, IL-2, IL-4, IL-6, IL-10, GM-CSF, or TGF-β levels.

Keywords

CD34+ cells Cytokines HNSCC patients Immunotherapy Vitamin D3 

Abbreviations

GM-CSF

granulocyte-macrophage colony-stimulating factor

high CD34+ patients

patients with greater than 1% baseline CD34+ cell levels

HLA

human leukocyte antigen

IFN

interferon

IL

interleukin

low CD34+ patients

patients with less than 1% baseline CD34+ cell levels

OD

optical density

TGF

transforming growth factor

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Deanne M. R. Lathers
    • 1
    • 3
  • Joseph I. Clark
    • 5
  • Nicholas J. Achille
    • 4
  • M. Rita I. Young
    • 1
    • 2
    • 3
  1. 1.Research Service (151)Ralph H. Johnson Veterans Affairs Medical CenterCharlestonUSA
  2. 2.Department of MedicineMedical University of South CarolinaCharlestonUSA
  3. 3.Department of OtolaryngologyMedical University of South CarolinaCharlestonUSA
  4. 4.Department of PathologyLoyola University Stritch School of MedicineMaywoodUSA
  5. 5.Cardinal Bernardin Cancer CenterLoyola University Stritch School of MedicineMaywoodUSA

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