Use of α,25-Dihydroxyvitamin D3 treatment to stimulate immune infiltration into head and neck squamous cell carcinoma

Prior studies have shown that treatment of head and neck squamous cell carcinoma (HNSCC) patients with 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] reduced intratumoral levels of immune inhibitory CD34(+) progenitor cells while increasing levels of mature progeny dendritic cells. This finding was extended to a pilot study to determine whether 1,25(OH)(2)D-3 treatment concurrently increases levels of intratumoral CD4(+) and CD8(+) T cells, increases intratumoral levels of immune cells expressing the early activation marker CD69, and prolongs time to HNSCC recurrence. The clinical trial comprised 16 patients with newly diagnosed HNSCC being untreated and 16 patients being treated with 1,25(OH)(2)D-3 during the 3-week interval between cancer diagnosis and surgical treatment. Immunologic effects of treatment were monitored by immunohistochemical analyses of surgically removed HNSCC. Clinical effectiveness of 1,25(OH)(2)D-3 treatment in this study was measured by the time to HNSCC recurrence. HNSCC tissues of patients who received treatment with 1,25(OH)(2)D-3 contained increased levels of CD4(+) cells and, more significantly, CD8(+) T cells. Also prominent was an increase in cells expressing the lymphoid activation marker CD69. Results of this pilot study suggest that patients treated with 1,25(OH)(2)D-3 had a lengthier time to tumor recurrence compared with patients who were not treated before surgery. Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics.