CAJ | 학술논문

目的：探讨半抗原二硝基氟苯（dinitrophenyl，DNP）修饰自体肿瘤疫苗在晚期恶性黑色素瘤治疗中的作用。方法84例Ⅲ期或Ⅳ期可切除恶性黑色素瘤患者随机分为半抗原DNP修饰瘤苗组和半抗原DNP未修饰瘤苗组，每组42例，分别采用半抗原DNP修饰的自体肿瘤疫苗和半抗原DNP未修饰的自体瘤苗联合化疗进行治疗，采用流式细胞技术检测两组患者外周血CD4+CD25+调节性T细胞（regulatory T cell，Treg）数量及淋巴细胞亚群的变化，观察迟发型超敏反应（delayed type hypersensitivity，DTH）及随访生存情况。结果治疗后半抗原DNP修饰瘤苗组患者CD4+-IFN-γPE、CD8+-IFN-γPE淋巴细胞亚群较治疗前及半抗原DNP未修饰瘤苗组明显升高（P均<0.05），而CD4+CD25+Treg数量减少（P<0.05），半抗原DNP未修饰瘤苗组治疗前后无明显变化（P>0.05）；半抗原DNP修饰瘤苗组患者较半抗原DNP未修饰瘤苗组DTH明显增强，硬结明显增大，两组DTH达到阳性结果（≥5 mm）的百分比分别为94.6%和45.0%（P<0.05）。半抗原DNP修饰瘤苗组患者1年、2年和3年生存率分别为95.0%、73.0%和65.5%，总生存率（overall survival，OS）为79.3%，无疾病生存率（disease free survival，DFS）为81.1%；半抗原DNP未修饰瘤苗组患者1年、2年和3年生存率分别为90.1%、59.0%和43.5%，OS为64.2%，DFS为74.0%，两组患者生存时间差异有统计学意义（P<0.05）。结论半抗原DNP修饰的自体瘤苗可增强恶性黑色素瘤患者特异性细胞介导的免疫反应，抑制机体免疫耐受，从而延长患者生存时间。
목적：탐토반항원이초기불분（dinitrophenyl，DNP）수식자체종류역묘재만기악성흑색소류치료중적작용。방법84례Ⅲ기혹Ⅳ기가절제악성흑색소류환자수궤분위반항원DNP수식류묘조화반항원DNP미수식류묘조，매조42례，분별채용반항원DNP수식적자체종류역묘화반항원DNP미수식적자체류묘연합화료진행치료，채용류식세포기술검측량조환자외주혈CD4+CD25+조절성T세포（regulatory T cell，Treg）수량급림파세포아군적변화，관찰지발형초민반응（delayed type hypersensitivity，DTH）급수방생존정황。결과치료후반항원DNP수식류묘조환자CD4+-IFN-γPE、CD8+-IFN-γPE림파세포아군교치료전급반항원DNP미수식류묘조명현승고（P균<0.05），이CD4+CD25+Treg수량감소（P<0.05），반항원DNP미수식류묘조치료전후무명현변화（P>0.05）；반항원DNP수식류묘조환자교반항원DNP미수식류묘조DTH명현증강，경결명현증대，량조DTH체도양성결과（≥5 mm）적백분비분별위94.6%화45.0%（P<0.05）。반항원DNP수식류묘조환자1년、2년화3년생존솔분별위95.0%、73.0%화65.5%，총생존솔（overall survival，OS）위79.3%，무질병생존솔（disease free survival，DFS）위81.1%；반항원DNP미수식류묘조환자1년、2년화3년생존솔분별위90.1%、59.0%화43.5%，OS위64.2%，DFS위74.0%，량조환자생존시간차이유통계학의의（P<0.05）。결론반항원DNP수식적자체류묘가증강악성흑색소류환자특이성세포개도적면역반응，억제궤체면역내수，종이연장환자생존시간。
Objective To investigate the efficacy of autologous tumor vaccine modified to carry the dinitrophenyl hapten to treat advanced malignant melanoma. Methods Clinical data were retrospectively analyzed for 84 patients who underwent resection for stageⅢb,Ⅲc or IV malignant melanomas. Patients were divided into two groups depending on whether or not their biochemotherapy was supplemented with dinitrophenyl-modified autologous tumor vaccine. The two groups were compared in terms of the following parameters:relative numbers of CD4+CD25+ regulatory T cells and lymphocyte subsets in peripheral blood,which were determined using flow cytometry;observed strength of delayed type hypersensitivity(DTH);and clinical outcomes such as overall survival(OS)and disease-free survival (DFS). Results The subpopulations of CD4+-IFN-γPE and CD8+-IFN-γPE lymphocytes were significantly larger in the vaccinated patients than in the biochemotherapy-only patients (P<0.05),while the relative proportions of CD4+CD25+ regulatory T cells were significantly smaller(P<0.05). DTH-positive response(defined as spot size ≥5 mm)occurred in 94.6% of vaccinated patients but in only 45% of biochemotherapy-only patients (P<0.05). The 1-,2- and 3-year survival rate were 95.0%,73.0 and 65.5% in the vaccinated group,respectively,90.1%,59.0%and 43.5% in the biochemotherapy-only group,respectively. OS and DFS in the vaccinated group were 79.3% and 81.1%,compared to 64.2% and 81.1% in the biochemotherapy-only group. The difference in OS between the two groups was significant (P<0.05). Conclusion Administering autologous tumor vaccine modified with the dinitrophenyl hapten may increase the overall survival of patients with specific cell-mediated melanoma,and it appears to do so by en-hancing their immune response and inhibiting immune tolerance.