首页|直肠癌患者外周血淋巴细胞亚群与新辅助治疗效果的关系

直肠癌患者外周血淋巴细胞亚群与新辅助治疗效果的关系

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目的 探讨直肠癌新辅助治疗对患者外周血淋巴细胞亚群绝对数和百分比的影响,及淋巴细胞亚群与新辅助治疗效果的关系.方法 回顾性分析2020年1月1日至2023年12月31日就诊于复旦大学附属肿瘤医院的局部晚期直肠癌患者外周血淋巴细胞亚群检测结果.入组患者均进行术前新辅助治疗[短程放疗序贯PD-1(程序性死亡受体1)单抗联合Xelox化疗4个疗程],在治疗前和新辅助治疗结束后都采用流式细胞术检测外周血中淋巴细胞各亚群(CD3+T、CD4+T、CD8+T、B、NK)的绝对数和比例(%)以及CD4+CD25+CD127low调节性T细胞(Treg)占CD4+T细胞的百分比(CD4+Treg%)、功能性CD8+T占总T细胞的百分比(CD8+CD28+T%).根据上述条件共有58例患者符合要求,并在完成新辅助治疗后,根据临床或病理诊断进行疗效判断,分为完全缓解(CR)组和非CR组,CR组男20例,女7例,年龄(52.89±9.95)岁;非CR组男17例,女14例,年龄(57.26±11.05)岁.采用配对t检验比较分析淋巴细胞各亚群在新辅助治疗前后的变化,通过两样本独立t检验分析CR组和非CR组各淋巴细胞亚群治疗后变化程度和治疗前基础水平的差异,并通过受试者工作特征(ROC)曲线评估相关亚群的基础水平对直肠癌患者新辅助治疗疗效的预测效能.把应用相同治疗方案但仅有治疗前淋巴细胞各亚群基础水平的患者(n=104)作为验证组,分析相关预测指标的符合率.结果 与新辅助治疗前比较,治疗后所有患者CD3+T、CD4+T、CD8+T、B、NK细胞绝对数均减少(P<0.05),CD8+T%和NK%均升高(P<0.05),B%下降(P<0.05),CD3+T%、CD4+T%、CD4+Treg%和 CD8+CD28+T%差异无统计学意义,上述变化与疗效无关,但CR组患者新辅助治疗前CD3+T、CD4+T、CD8+T绝对数,CD3+T%、CD8+T%以及CD8+CD28+T%高于非CR组患者(P<0.05).ROC曲线分析显示,上述疗效相关指标治疗前基础值预测直肠癌患者新辅助治疗完全缓解与否的曲线下面积(AUC)分别为0.838、0.756、0.839、0.659、0.702、0.858;其中,CD3+T绝对数联合CD8+CD28+T%检测的AUC为0.886,敏感度和特异度分别为81.5%和90.3%.在验证组中,上述预测指标的阳性符合率为69.4%~97.5%,阴性符合率为69.8%~84.4%.结论 直肠癌新辅助治疗影响淋巴细胞的组成比,使具有抗肿瘤效应的免疫细胞比例增加,且可通过患者治疗前的淋巴细胞亚群数量和组成比预测新辅助治疗的疗效.
Relationship between peripheral blood lymphocyte subsets and neoadjuvant therapy efficacy in patients with colorectal cancer
Objective To investigate the impact of neoadjuvant therapy on the absolute counts and percentages of peripheral blood lymphocyte subsets in rectal cancerpatientsand examine the relationship between the efficacy of neoadjuvant therapy and lymphocyte subsets.Methods A retrospective analysis was conducted on locally advanced rectal cancer patients treated at Fudan University Shanghai Cancer Center from January 1,2020 to December 31,2023.All enrolled patients received preoperative neoadjuvant therapy[short-course radiotherapy followed by four cycles of PD-1(programmed cell death protein 1)monoclonal antibody combined with Xelox chemotherapy].Flow cytometry was used before and after neoadjuvant therapy to assess the absolute counts and percentages of peripheral blood lymphocyte subsets,including CD3+T cells,CD4+T cells,CD8+T cells,B cells,NK cells,as well as the percentage of CD4+CD25+CD127low regulatory T cells within CD4+T cells(CD4+Treg%)and the percentage offunctional CD8+T cells withintotalTcells(CD8+CD28+T%).Based on these criteria,58 patients were eligible for the study.Following neoadjuvant therapy,therapeutic efficacy was evaluated through clinical and pathological diagnosis,classifying patients intoa complete response(CR)group(including clinical complete response and pathologic complete response)and non-CR group.The CR group consisted of 20males and 7 females(mean age 52.89±9.95 years),while the non-CR group included 17males and 14 females(mean age 57.26±11.05 years).Paired t-test were used to compare changes in lymphocyte subsets before and after neoadjuvant therapy,and independent two-sample-t-tests were applied to analyze the differences in post-treatment changes and the basal levels of lymphocyte subsets between CR group and non-CR group.Receiver operating characteristic(ROC)curve were employed to evaluate the predictive performance of baseline lymphocyte subsets for the efficacy of neoadjuvant therapy in rectal cancer patients.A validation cohort(n=104)with only baseline lymphocyte subset data was used to assess the coincidence of the predictive indicators.Results After completion of neoadjuvant therapy,all patients showed a reduction in the absolute counts of CD3+T,CD4+T,CD8+T,B and NK cells(P<0.05),with an increase in CD8+T%and NK%(P<0.05),and a decrease in B%(P<0.05).No statistically significant differences were observed in CD3+T%,CD4+T%,CD4+Treg%and CD8+CD28+T%.These changes were independent of therapeutic efficacy,however,baseline levels of CD3+T,CD4+T,CD8+T absolute counts,as well as CD3+T%,CD8+T%and CD8+CD28+T%,were significantly higher in the CR group than in the non-CR group(P<0.05).ROC curve analysis of these efficacy-related baseline indicators showed areas under the curve(AUC)of 0.838,0.756,0.839,0.659,0.702 and 0.858,respectively.Combining CD3+T absolute count with CD8+CD28+T%yielded an AUC of 0.886,with a sensitivity of 81.5%and specificity of 90.3%.In the validation cohort,the positive predictive consistency for these indicators ranged 69.4%to 97.5%,while negative predictive consistency ranged from 69.8%to 84.4%.Conclusions Neoadjuvant therapy for rectal cancer affects the ratio of lymphocytes,elevates the proportion of immune cells with anti-tumor effects.The number and ratio of lymphocyte subsets before treatment can predict the efficacy of neoadjuvant therapy for rectal cancer.

Colorectal cancerNeoadjuvant therapyLymphocyte subsetsEfficacy prediction

陈颖秀、卢仁泉、郭林、郑慧

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复旦大学附属肿瘤医院厦门医院检验科,厦门 361022

复旦大学附属肿瘤医院检验科,上海 200032

直肠癌 新辅助治疗 淋巴细胞亚群 疗效预测

2024

中华检验医学杂志
中华医学会

中华检验医学杂志

CSTPCD北大核心
影响因子:1.402
ISSN:1009-9158
年,卷(期):2024.47(12)