Cancer Immunology, Immunotherapy

, Volume 53, Issue 5, pp 422–430 | Cite as

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. YoungEmail author
Original Article


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.


CD34+ cells Cytokines HNSCC patients Immunotherapy Vitamin D3 



granulocyte-macrophage colony-stimulating factor

high CD34+ patients

patients with greater than 1% baseline CD34+ cell levels


human leukocyte antigen





low CD34+ patients

patients with less than 1% baseline CD34+ cell levels


optical density


transforming growth factor



This work was supported by grants from the Medical Research Service of the Department of Veterans Affairs (M.R.I.Y., D.M.R.L.), and by Grants R01-CA85266, R01-CA45080 and R21-CA77108 from the National Institutes of Health (M.R.I.Y.). We gratefully acknowledge the contributions to these studies by the nursing staff of 11 West at the Hines VA Hospital, the laboratory staff at the Cardinal Bernardin Cancer Center of Loyola University Medical Center, and the Hematology/Oncology Clinical Research Nurses at Loyola University Medical Center and the Hines VA Hospital.


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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
    Email author
  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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