Immunological modulation by 1α,25-dihydroxyvitamin D3 in patients with squamous cell carcinoma of the head and neck

Prior studies showing that treatment of head and neck squamous cell carcinoma (HNSCC) patients with 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] stimulated intratumoral immune infiltration were extended to analysis of cytokine profiles in the periphery and in oral tissues. Most prominent was the disparity between cytokine levels in plasma and in either pathologically normal oral tissue or HNSCC tissue from patients that were untreated or treated with 1,25(OH)2D3. Levels of IL-6 and IL-10, but not IL-2, IFN-γ or TNF-α, tended to be increased in the plasma of HNSCC patients and 1,25(OH)2D3 further increased plasma levels of all of these cytokines. While these cytokines tended to be increased in HNSCC tissue, 1,25(OH)2D3 resulted in variable cytokine responses that showed a general tendency toward further increased levels. Levels of IL-8 and VEGF were increased in plasma and tissue of untreated HNSCC patients, and were further increased in plasma, but not in tissues, of patients treated with 1,25(OH)2D3. Levels of IL-1α and IL-1β were similar in plasma of controls and HNSCC patients, but were increased in HNSCC tissues. In contrast to that seen in plasma where 1,25(OH)2D3 increased levels of IL-1α and IL-1β, this was not seen in tissue following 1,25(OH)2D3 treatment. These results show a discordant relationship between systemic and intratumoral cytokine profiles and suggest a tendency of 1,25(OH)2D3to increase a multitude of cytokines within tumor tissue.

► Head and neck cancer tissue contains a cytokine-stimulated environment. ► Vitamin D treatment of HNSCC patients increases Th1 and Th2 cytokines. ► Vitamin D does not stimulate VEGF, IL-8, IL-1α or IL-1β in HNSCC tissue. ► Systemic cytokine levels do not parallel oral tissue cytokine levels.