Results of the study of mucosal immunity indices in patients with cancer of the oral cavity and oropharynx during radiotherapy or chemoradiotherapy therapy and immunotherapy with α/β-defensins.

Background: The aim of the study was to investigate the concentration of interferon (INF) -a, INF- g, interleukin (IL) -6, and secretory IgA (sIgA) in saliva during various regimens of antitumour treatment and immunotherapy (IT) with a/b-defensins in patients with cancer of the oral cavity and oropharynx in order to find ways to increase the effectiveness and improvement of the tolerability of antitumour treatment on the base of the identification of biomarkers for the evaluation of the antitumour effect and the prediction of complications.

Materials and methods: We have studied the changes in the immunity indices of 105 patients who were diagnosed with squamous cell carcinoma of the oral cavity or oropharynx for the first time. The patients received radiotherapy (RT) or chemoradiotherapy and IT with a/b-defensins in different doses (40 and 60 mg) at the 1st phase of the special treatment.

Results: A determined drop in the concentration of INF-a after cytostatic treatment, and the additional use of IT with a/b-defensins in different doses do not produce the protective effect on the production of INF-a. Regarding INF- g, a more than two-fold decrease in the concentration of INF- g in the saliva of patients in group receiving a double dose of an immunotherapeutic agent along with radiation therapy (RT) was noted, which may indicate an adjuvant effect of a/b-defensins in relation to RT, enhancing its antitumour influence, and thereby ensuring the regression of neoplasia. In case of an increased dose of a/b-defensins use during RT, there was found immunomodulatory effect in relation to IL-6. In the group of patients who received RT and a higher dose of the immune agent, the "scissors phenomenon" was noted - a simultaneous decrease in the concentration of INF- g and an increase in the concentration of sIgA in saliva, which, taking into account the reduced risk of mucositis and better regression of the tumour, shows the meaningful adjuvant and immunomodulating effects of a/b-defensin therapy in the study group.

Conclusion: High-dose IT with a/b-defensins against the background of cytostatic therapy in patients with cancer of the oral cavity and oropharynx potentially leads to an adjuvant and immunomodulatory effect with a decrease in the concentration of INF- g and a parallel increase in the concentration of sIgA in saliva, i.e., reconstruction of the immune response from Th1- to Th2-profile - the profile associated with the tumour regression. With the development of the radio-induced mucositis in these patients, a decrease in concentration of sIgA in saliva with a tendency to a progressive decrease of this index with the increase of mucositis severity was noted. The data obtained allow us to consider INF- g and sIgA as biomarkers of the effectiveness of traditional anticancer therapy during the use of a/b-defensins, and sIgA as a biomarker of the risk of developing radio-induced mucositis in patients with cancer of the oral cavity and oropharynx, which should be verified in further clinical studies with better design.