RESUMO
It has been shown that head and neck squamous cell carcinoma (HNSCC) are infiltrated by plasmacytoid dendritic cells (pDCs). The HNSCC TH2 biased microenvironment leads to strong alterations of the cellular functions of pDC and thus impairs the initiation and function of adequate immune responses. In this work we comprehensively analyzed the capacity of CpG-oligonucleotides to activate interferon (IFN)-α secretion of human pDC in the presence of HNSCC. IFN-α secretion was measured using the ELISA Technique. Class A CpG dinucleotide 2216 was used in different concentrations and time frames to stimulate the IFN-α production of human pDC from peripheral blood in the absence and presence of the HNSCC microenvironment. To elucidate single components that might induce the reduction of IFN-α secretion, pDC were exposed to different concentrations of HNSCC relevant cytokines such as IL-6, IL-8 and IL-10. In accordance to former experiments we found that HNSCC micro milieu severely depresses up to 75% of IFN-α secretion capacity of pDCs, if the stimulating Class A CpG 2216 is added to the culture. Preincubation of HNSCC supernatant leads to unrestorable reduction of IFN-α secretion in pDC and can not be restored by CpG 2216. Incubation of pDCs with single cytokines relevant for cancer progression within the HNSCC micro milieu show that IL-6 or IL-8 have no influence on the IFN-α secretion in pDCs, whereas IL-10 massively impairs the secretion in a dose dependent manner. This effect can be potentiated by synergistic incubation with IL-6 and can be abrogated by blocking antibodies to the IL-10 receptor. Interestingly, incubation with IL-10 is not the only factor that impairs the IFN-α secretion, as incubation with the whole HNSCC supernatant is even more effective in reducing the secretion, implying that additional factors play a role. We conclude that restoration of HNSCC induced TH2 bias could be improved by the inhibition of immune cell cytokine receptors in addition to immunostimulating approaches with CpG motifs.
RESUMO
BACKGROUND/AIM: During the treatment of head and neck cancer (HNC), salivary problems may impair a patient's healing process. Botulinum toxin (BoNT) is accepted as an effective treatment option for reducing salivary flow. We aimed to describe the features of patients treated with BoNT to determine the effects of BoNT. PATIENTS AND METHODS: Twenty-five patients over a five-year period were retrospectively included. The patients suffered at different stages of oncologic treatment. The cohort primarily had larger primary tumors that required complex oncological treatment. RESULTS: The condition improved in more than three quarters of the 19 patients with functional hypersalivation. Four of six cases suffering from a salivary fistula demonstrated an obvious reduction in symptoms. CONCLUSIONS: Injection of BoNT, to temporarily reduce saliva flow, is a safe tool in the treatment of HNC even in situations involving repeated therapy or high dosage. The main clinical side-effect of BoNT is insufficient reduction of the salivary problem.