Abstract
Problem
Quantitate the intratumoral differentiation of HNSCC induced immunoinhibitory CD34+ in response to enteral treatment of 1,25 dihydroxyvitamin D3 (1,25D3).
Methods
8 patients with HNSCC were treated orally with 3 weeks of 1,25D3 before surgical excision. Tumor tissue was collected and analyzed using immunohistochemistry to test the hypothesis that treatment would drive differentiation of immune inhibitory CD34+ cells into immune stimulatory dendritic cells. Patients’ clinical data for high risk pathological features were also analyzed.
Results
After 1,25D3 treatment, intratumoral levels of CD34+ cells significantly dropped. Levels of DC-lamp, a cellular marker for mature dendritic cells, significantly increased while there was not a change in intratumoral levels immature dendritic cell marker DC-sign. Levels of CD4+ cells were unchanged while levels of CD8+ cells were significantly decreased. There were no associated statistically significant correlations between CD34+ levels and histological features, although there was a trend of increasing cervical metastasis in patients with increased intratumoral CD34+ cells.
Conclusion
CD34+ cells are hematopoietically immature cells that have been shown to differentiate to dendritic cells when grown in culture. This is the first study to analyze the effects of enteral 1,25D3 on intratumoral immune infiltrate, specifically CD34+ cells. 1,25D3 stimulated differentiation of CD34+ immunosuppressive cells to differentiate into immunostimulatory dendritic cells.
Significance
Despite recent advances in treatment, patients with HNSCC have a five year mortality rate of less than 50%. One aspect contributing to the poor prognosis is the profound immunoinhibitory effects induced by HNSCC. It has been shown that CD34+ suppressor cells are a component of this immunosuppresion induced by the carcinoma. Adding 1,25D3 in the treatment of HNSCC decreased levels of intratumoral CD34+ cell population and diminish the profound immunoinhibitory effects of the cancer. These studies support the use of 1,25D3 as a neo-adjunctive therapy to overcome HNSCC profound immunosuppression thereby potentiating other promising immunotherapies.
Support
Clinical Sciences Research Service, Department of Veterans Affairs, Washington, D.C. Vitamin D therapy to enhance intratumoral anti-cancer immune reactivity October 2004 - September 2009 $747,000; University Research Committee Resident Research Grant, Medical University of South Carolina January 2008 $2,000.
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