HLA-A0201阳性慢性粒细胞白血病PR1特异性细胞毒性T细胞的初步研究

目的 探讨PR1特异性细胞毒性T细胞(CTL)与HLA-A0201阳性慢性粒细胞白血病(CML)患者疗效及预后的关系,探讨是否可以应用PR1肽作为疗效达到停药试验标准患者的后续免疫治疗,从而维持长期缓解状态.方法 收集28例HLA-A0201阳性CML患者外周血,利用可溶性PR1-MHC-Ⅰ类四聚体技术及流式细胞术检测PR1特异性CTL存在与否、频率高低;比较不同治疗时间CML患者PR1特异性CTL表达的差异.结果 PR1特异性CTL频率与同期PCR(bcr-abl/abl)IS(IS:国际标准值)之间呈负相关(r=-0.658,P＜0.001).接受治疗3、6、9个月及1、2、3、4、5、6年的PR1特异性CTL频率分别为(0.06±0.02)％、(0.10±0.02)％、(0.14土0.02)％、(0.16±0.02)％、(0.20±0.03)％、(0.18±0.03)％、(0.18±0.01)％、(0.17±0.05)％、(0.18±0.03)％.治疗3、6、9个月的频率分别与其他时间点频率相比,差异均有统计学意义(均P＜ 0.05).治疗1年及以上的频率两两相比,差异均无统计学意义(均P＞0.05).伊马替尼400 mg 1次/d治疗3、6、9、12个月,Sokal评分高危组患者PR1特异性CTL频率低于低危组、中危组.结论 治疗效果显著的CML患者体内可持续检测到PR1特异性CTL,其与肿瘤负荷呈负相关,提示PR1特异性CTL可能与抗白血病细胞作用相关,为疗效获得持续稳定MR4-5及MR5.0的CML患者使用PR1肽疫苗作为后续免疫治疗提供了依据.

Research on PR1 specific cytotoxic T lymphocytes of HLA-A0201 positive chronic myelogenous leukemia

Objective To evaluate the relationship between proportion of PR1 specific cytotoxic T lymphocytes (CTLs) in the peripheral blood and prognosis and curative effect in patients with HLA-A0201 positive chronic myelogenous leukemia (CML),and to discuss whether PR1 peptide could be used as the following immune therapeutic method for patients who had achieved the standard of stop treatment.Methods The soluble HLA-A0201/PR1 tetramer and flow cytometry were applied to determine the proportion and the frequency of PR1 specific CTLs in peripheral blood from 28 HLA-A0201 positive CML patients.The proportions were compared among different phases of patients.The correlations between the proportion of PR1 specific CTLs and clinical parameters were analyzed.Results There was a negative correlation between PR1 specific CTLs and PCR (bcr-abl/abl)Is (r =-0.658,P ＜ 0.001).The frequencies of PR1 specific CTLs at 3-month,6-month,9-month,12-month,2-year,3-year,4-year,5-year,6-year were (0.06±0.02) ％,(0.10± 0.02) ％,(0.14±0.02) ％,(0.16±0.02) ％,(0.20±0.03) ％,(0.18±0.03) ％,(0.18±0.01) ％,(0.17±0.05) ％ and (0.18±0.03) ％,respectively.The frequency of PR1 specific CTLs at 3-month,6-month or 9-month was statistically different compared with that of the other time spots (P ＜ 0.05),and there were no statistical differencies among the frequencies at 1-year,2-year,3-year,4-year,5-year,6-year (P ＞ 0.05).For patients treated with IM 400 mg qd,the frequency of PR1 specific CTLs in high-risk group was lower than that in low-risk or intermediate-risk groups.Conclusion PR1 specific CTLs can be detected in patients who achieved good curative effect,and is correlated with tumor burden,which indicates that PR1 specific CTLs may be related to the action of resisting leukemia and provide the evidence for PR1 peptide as a potential immune therapeutic schedule in patients who have achieved stable MR45 and MR50.