Klin Onkol. 2023 Spring;36(2):112-123. doi: 10.48095/ccko2023112.
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.
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.
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.
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.
本研究的目的是探讨在口腔和口咽癌患者的各种抗肿瘤治疗和免疫治疗（IT）方案中，干扰素（INF）-a、INF-γ、白细胞介素（IL）-6 和分泌型免疫球蛋白 A（sIgA）在唾液中的浓度，以便在确定抗肿瘤作用的生物标志物的基础上找到增加抗肿瘤治疗效果和改善耐受性的方法，并预测并发症。
我们研究了 105 例首次被诊断为口腔或口咽鳞状细胞癌的患者的免疫指标变化。这些患者在特殊治疗的第 1 阶段接受了不同剂量（40 和 60mg）的 a/b-防御素的放疗（RT）或放化疗和 IT。
细胞毒性治疗后，INF-a 的浓度明显下降，额外使用不同剂量的 a/b-防御素进行 IT 治疗并没有对 INF-a 的产生产生保护作用。关于 INF-γ，我们注意到接受双倍剂量免疫治疗药物联合放疗（RT）的患者唾液中 INF-γ 的浓度下降了两倍多，这可能表明 a/b-防御素与 RT 之间具有辅助作用，增强了其抗肿瘤作用，从而确保肿瘤消退。在 RT 期间增加 a/b-防御素的使用剂量时，发现其对 IL-6 具有免疫调节作用。在接受 RT 和更高剂量免疫剂的患者组中，我们观察到了“剪刀现象”——INF-γ 浓度同时下降，唾液中 sIgA 浓度增加，这考虑到粘膜炎风险降低和肿瘤更好地消退，表明 a/b-防御素治疗在研究组中具有有意义的辅助和免疫调节作用。
在口腔和口咽癌患者中，在细胞毒性治疗的基础上进行高剂量 IT 治疗与 IFN-γ 浓度降低和唾液中 sIgA 浓度平行增加有关，即从 Th1 向 Th2 谱的免疫反应重建 - 与肿瘤消退相关的谱。在这些患者中发生放射性粘膜炎时，我们注意到唾液中 sIgA 的浓度下降，并且随着粘膜炎严重程度的增加，该指数呈下降趋势。获得的数据使我们能够将 IFN-γ 和 sIgA 视为使用 a/b-防御素时传统抗癌治疗效果的生物标志物，并将 sIgA 视为口腔和口咽癌患者发生放射性粘膜炎风险的生物标志物，这需要在进一步的临床研究中进一步验证，以设计更好。
