食管癌患者化疗联合细胞免疫治疗前后外周血淋巴细胞亚群变化的分析

目的:探讨肿瘤分期和治疗对食管癌患者外周血淋巴细胞亚群的影响及其相应的临床意义。方法:选取在我院治疗的113例食管癌患者，其中45例中晚期患者接受了化疗联合细胞免疫治疗。对113例患者进行了治疗前外周血淋巴细胞亚群检测，对45例患者进行了联合治疗前后外周血淋巴细胞亚群、肿瘤标志物检测。分析细胞免疫治疗周期、疗效与外周血淋巴细胞亚群的相关性以及治疗前肿瘤血清学标志物与疗效的相关性。结果:早期食管癌患者CD8+/CD28+T细胞(Tc)比例高于中晚期患者，CD4+/CD25+T细胞(Treg)比例低于中晚期患者（P=0.011、P=0.015）。45例患者治疗后CD3+T细胞(TT)、Tc、髓系树突状细胞(mDCs)比例明显升高（P=0.003、P=0.039、P=0.007）。细胞免疫治疗1个周期14例（A组），2个周期16例（B组），3个周期及以上15例（C组）。A组患者治疗后TT比例明显升高，Treg比例明显下降；B组患者治疗后TT、Tc比例明显升高；C组患者发现了三组淋巴细胞亚群的变化，其中TT、Treg比例变化较A、B两组更为显著（P=0.003 7、P=0.002）。30例获得客观缓解的患者治疗后TT、Tc、自然杀伤T细胞(NKT)和mDCs比例较治疗前明显升高，而Treg比例则较前明显下降。治疗前鳞状上皮细胞癌相关抗原（SCC）正常的患者客观缓解率要好于升高的患者（P=0.029）。结论:中晚期食管癌患者较早期患者免疫失衡更为明显，细胞免疫治疗联合化疗可以改善食管癌患者的免疫状态，治疗效果与患者的免疫功能改善程度有关，SCC升高可能影响食管癌患者的近期疗效。

Analysis of peripheral blood lymphocyte sub-populations variations in patients with esophageal cancer when chemotherapy combined with cellular immunotherapy

Objective:To investigate the comparative changes of peripheral blood lymphocyte sub-populations during the entire cycle of chemotherapy combined with autologous adoptive T cell immunotherapy among the esophageal cancers and associated clinical significances.Methods:A total of 113 patients with esophageal cancer who were treated in our hospital were selected.Among them,45 advanced patients received chemotherapy combined with cellular immunotherapy.Peripheral blood lymphocyte subsets were detected in 113 patients before treatment and peripheral blood lymphocyte subsets and tumor biomarkers were detected before and after combined treatment in 45 patients.The correlations were analyzed between cell treatment cycle and peripheral blood lymphocyte subsets,efficacy and peripheral blood lymphocyte subsets,as well as the correlation was analyzed between tumor serological markers and efficacy before treatment.Results:CD8+/CD28+T cell(Tc) was higher in early esophageal cancer patients than in advanced esophageal cancer patients,and CD4+/CD25+T cell（Treg) was lower than in advanced esophageal cancer patients（P values were 0.011 and 0.015,respectively).CD3+T cell(TT),Tc,and myeloid dendritic cells（mDCs) were significantly increased in 45 patients after treatment（P=0.003,P=0.039,P=0.007).Cell immunotherapy was performed in 14 patients with 1 cycle（group A),16 patients with 2 cycles（group B),and 15 patients with 3 cycles or more（group C).TT was significantly increased and Treg was significantly decreased in group A after treatment,TT and Tc were significantly increased in group B after treatment,and changes in three lymphocyte subsets were found in group C,with TT and Treg changes were more significant than those in A,B groups（P=0.003 7,P=0.002).Inthirty patients who achieved objective remission,TT,Tc,natural killer T cell(NKT) and mDCs were significantly increased after treatment while Treg was significantly decreased after treatment.Patients with normal squamous cell carcinoma-associated antigen(SCC) before treatment had better objective response rate than those with increased SCC（P=0.029).Conclusion:The immune unbalance in patients with advanced esophageal cancer is more prevalent than that in patients with early esophageal cancer.Cellular immunotherapy combined with chemotherapy can improve the immune status of patients with esophageal cancer,and the therapeutic effect is related to the improvement of patients' immune function.The increase of SCC may affect the short-term efficacy of patients with esophageal cancer.