Chen Xi, Zhang Wencheng, Qian Dong, Guan Yong, Wang Yuwen, Zhang Hualei, Er Puchun, Yan Cihui, Li Yueguo, Ren Xiubao, Pang Qingsong, Wang Ping
>Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Department of Immunology,Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Front Oncol. 2019 Feb 15;9:73. doi: 10.3389/fonc.2019.00073. eCollection 2019.
Chemoradiotherapy (CRT) is an important component of treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Recent research findings support the role of CRT in activating an anti-tumor immune response. However, predictors of CRT efficacy are not fully understood. The aim of this study was to measure CRT-induced changes to lymphocyte subpopulations and to evaluate the prognostic value of lymphocyte alterations for patients with ESCC. In total, this pilot study enrolled 64 patients with ESCC who received neo-adjuvant CRT or definitive CRT. Peripheral blood samples were collected before and during treatment and were analyzed by flow cytometry for CD19, CD3, CD4, CD8, CD56, and CD16. Relationships between lymphocyte subset alterations and overall survival (OS) and progression-free survival (PFS) were evaluated using the log-rank test and a Cox regression model. The median follow-up period was 11.8 months (range, 4.0-20.2 months). Compared to pre-treatment specimens, post-treatment blood samples had decreased proportions of CD19 B-cells and increased proportions of CD3 and CD8 T-cells (all < 0.05). Univariate and multivariate analysis showed that increased CD4 T-cell ratios after CRT independently predicted superior PFS (hazard ratio [HR] = 0.383; 95% confidence interval [CI] = 0.173-0.848, = 0.017) and that increased CD8 T-cell ratios predicted improved OS (HR = 0.258; 95% CI = 0.083-0.802, = 0.019). Patients with both increased CD4 and CD8 ratios had a superior PFS and OS, compared to patients with an increased CD4 ratio only or CD8 ratio only or neither (1-year PFS rate 63 vs. 25%, 1-year OS rate 80 vs. 62%, = 0.005 and 0.025, respectively). CRT-induced increases in CD4 and CD8 T-cell ratios are reliable biomarker predictors of survival in patients with ESCC.
放化疗（CRT）是局部晚期食管鳞状细胞癌（ESCC）患者治疗的重要组成部分。最近的研究结果支持了CRT在激活抗肿瘤免疫反应中的作用。然而，CRT疗效的预测指标尚未完全明确。本研究的目的是检测CRT诱导的淋巴细胞亚群变化，并评估淋巴细胞改变对ESCC患者的预后价值。本前瞻性研究共纳入64例接受新辅助CRT或根治性CRT的ESCC患者。在治疗前和治疗期间采集外周血样本，通过流式细胞术分析CD19、CD3、CD4、CD8、CD56和CD16。使用对数秩检验和Cox回归模型评估淋巴细胞亚群改变与总生存期（OS）和无进展生存期（PFS）之间的关系。中位随访期为11.8个月（范围4.0 - 20.2个月）。与治疗前标本相比，治疗后血样中CD19 B细胞比例降低，CD3和CD8 T细胞比例升高（均P < 0.05）。单因素和多因素分析显示，CRT后CD4 T细胞比例升高独立预测较好的PFS（风险比[HR] = 0.383；95%置信区间[CI] = 0.173 - 0.848，P = 0.017），CD8 T细胞比例升高预测OS改善（HR = 0.258；95% CI = 0.083 - 0.802，P = 0.019）。与仅CD4比例升高或仅CD8比例升高或两者均未升高的患者相比，CD4和CD8比例均升高的患者具有更好的PFS和OS（1年PFS率63%对25%，1年OS率80%对62%，P分别为0.005和0.025）。CRT诱导的CD4和CD8 T细胞比例增加是ESCC患者生存的可靠生物标志物预测指标。
