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。
Anti-tunor immunological response induced by local intervention is ideal for treatment of metastatic tumors.Laser immunot herapy was developed to synergize photot hermal interaction with immunological stimulation for cancer treatment.Using an infrared laser,indocyanine green(ICG,as a light abeorbing agent),and glycated chitosan(GC,as an immunostimulant),.laser imm unot herapy has resulted in tumor suppression and anti-tumor responses in pre-clinical as well as clinical studies.To further understand the mechanism of laser immunotherapy,the efects of laser and GC treatment without specifc enhancement of laser absorption were studied.Passive adoptive immunity transfer was perfomed using splenocytes as immune cells.Spleen cells harvested from tumor-bearing mice treated by laser+GC provided 60%immunity in naive recipients.Furthermore,cytotoxicity and TNF-ar secretion by splenocytes from treated mice also indicated that laser+GC induced immunity was tumor-specific.The high level of infiltrating T cells in tumors after laser+GC treatment furt her confirned a specific anti-tumor immune response.Therefore,laser+GC could prove to be a promisi ng selective local trea tment modality that induces a systemic anti-tumor response,with appropriate laser parameters and GC doses.
