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目的冷冻手术联合过继细胞免疫可能提供一种新的口腔黏膜恶性黑色素瘤的综合治疗方法。本研究通过监测冷冻联合改良的细胞因子诱导杀伤细胞(improved cytokine induced killer cells,iCIK)治疗口腔恶性黑色素瘤患者的外周血T细胞免疫变化和临床疗效,探讨外周血来源的iCIK细胞辅助冷冻治疗的安全性、有效性和免疫学机制。方法应用流式细胞术对2009年10月以来中山大学附属口腔医院应用iCIK辅助冷冻手术治疗的5例Ⅲ期以上口腔黏膜恶性黑色素瘤患者进行定期复诊研究,分析iCIK辅助冷冻手术对患者外周血T细胞功能和体外T细胞激活的影响,评价其临床疗效及不良反应。结果 5例患者治接受冷冻手术9次,iCIK细胞免疫治疗43次。本研究对冷冻手术治疗前后患者外周血T细胞激活的比较研究显示冷冻治疗显著增加了CD3+T细胞,CD3+CD4+Th细胞及CD3+CD8+CTL的细胞比例,提高了IL2,IFN-γ,TNF-α等Th1细胞因子的分泌。iCIK治疗前后的T细胞激活检测显示了类似的结果,表明这两种治疗可以促进患者T细胞免疫功能的激活(P<0.05)。这些患者外周血免疫分析显示iCIK辅助冷冻治疗显著地提高了血液中T,Th及CTL细胞比例和Th1细胞因子的分泌,降低Treg细胞比例,进一步提供了iCIK辅助冷冻治疗能有效地改善患者T细胞免疫功能的证据。临床随访资料显示冷冻手术结合iCIK治疗5名口腔黏膜恶性黑色素瘤中,除一例患者生存9个月以外,4例患者目前均存活,且生存期分别为41+、39+、39+和31+个月,无明显不良反应。结论冷冻结合iCIK治疗口腔恶性黑色素瘤可以显著改善患者的T细胞免疫状况,是一种安全有效的综合治疗。
Objective Cryotherapy combined with adoptive cell immunotherapy may provide a new comprehensive treatment of oral mucosal malignant melanoma. In this study, peripheral blood T cell immune changes and clinical efficacy in patients with oral malignant melanoma treated by cryotherapy combined with improved cytokine induced killer cells (iCIK) were monitored to investigate the effects of peripheral blood-derived iCIK cells assisted by cryo-therapy Safety, efficacy and immunological mechanisms. Methods Flow cytometry was used to perform regular follow-up study on 5 cases of stage III or more patients with oral mucosal malignant melanoma treated with iCIK-assisted cryosurgery affiliated to Stomatological Hospital of Sun Yat-sen University from October 2009 to October 2009. The results of iCIK assisted cryosurgery on peripheral blood T Cell function and in vitro T cell activation, evaluate its clinical efficacy and adverse reactions. Results Five patients underwent cryotherapy for 9 times and iCIK cells for 43 times. In this study, we compared the activation of T cells in peripheral blood before and after cryosurgery, and found that cryotherapy significantly increased the proportion of CD3 + T cells, CD3 + CD4 + Th cells and CD3 + CD8 + CTL cells, and increased the levels of IL2, IFN- γ , TNF-α and other Th1 cytokine secretion. Tests of T cell activation before and after iCIK treatment showed similar results, indicating that both treatments promoted activation of T cell immune function in patients (P <0.05). Immunohistochemical analysis of peripheral blood in these patients showed that iCIK-assisted cryotherapy significantly increased the proportion of T, Th and CTL cells and Th1 cytokines in the blood, decreased the proportion of Treg cells, and further provided iCIK-assisted cryotherapy to effectively improve T cells in patients Evidence of immune function. Clinical follow-up data showed that in all 5 oral malignant melanomas treated with cryotherapy combined with iCIK, 4 patients survived for 9 months except for one patient, and the survival rates were 41 +, 39 +, 39 + and 31+, respectively Month, no significant adverse reactions. Conclusion Combined with iCIK in the treatment of oral malignant melanoma can significantly improve the patient’s immune status of T cells, which is a safe and effective combination therapy.