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

Authors

  • Deanne M. R. Lathers
    • Research Service (151)Ralph H. Johnson Veterans Affairs Medical Center
    • Department of OtolaryngologyMedical University of South Carolina
  • Joseph I. Clark
    • Cardinal Bernardin Cancer CenterLoyola University Stritch School of Medicine
  • Nicholas J. Achille
    • Department of PathologyLoyola University Stritch School of Medicine
    • Research Service (151)Ralph H. Johnson Veterans Affairs Medical Center
    • Department of MedicineMedical University of South Carolina
    • Department of OtolaryngologyMedical University of South Carolina
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

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+ cellsCytokinesHNSCC patientsImmunotherapyVitamin 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