He Chaobin, Wang Jun, Sun Shuxin, Zhang Yu, Li Shengping
Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Department of Ultrasonics, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
J Oncol. 2019 May 12;2019:9346017. doi: 10.1155/2019/9346017. eCollection 2019.
Irreversible electroporation (IRE) has been demonstrated to be a safe and effective method for locally advanced pancreatic cancer (LAPC). The aim of this study was to evaluate the immunomodulatory effect after IRE and to evaluate the prognostic value of variations of the immune parameters in LAPC patients after IRE.
Peripheral blood samples of 34 patients were obtained preoperatively and on the third day (D3) and seventh day (D7) after IRE, respectively. The phenotypes of lymphocytes were analyzed by flow cytometry, and dynamic changes of serum levels of cytokines, complement, and immunoglobulin were assayed by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve and concordance index (C-index) were used to compare the survival predictive ability.
There was a transitory decrease followed by a steady increase for CD4 T cell, CD8 T cell, NK cell, IL-2, C3, C4, and IgG while a reverse trend was detected for Treg cell, IL-6, and IL10 after IRE. The alteration of CD8 T cell between D3 and D7 was identified as a prognostic factor for both overall survival (OS) and progression-free survival (PFS). The values of ROC curve (AUC) and C-indexes of the alteration of CD8 T cell for OS and PFS were 0.816 and 0.773 and 0.816 and 0.639, respectively, which were larger than those of other immune or inflammation-based indexes.
This study presented the first evidence of IRE-based immunomodulatory in patients with LAPC. The alteration of CD8 T cell between D3 and D7 showed relatively good performance and could be used as an effective tool for prognostic evaluation for LAPC patients after IRE.
不可逆电穿孔(IRE)已被证明是治疗局部晚期胰腺癌(LAPC)的一种安全有效的方法。本研究的目的是评估IRE后的免疫调节作用,并评估IRE后LAPC患者免疫参数变化的预后价值。
分别在术前以及IRE后的第三天(D3)和第七天(D7)采集34例患者的外周血样本。通过流式细胞术分析淋巴细胞表型,采用酶联免疫吸附测定法检测细胞因子、补体和免疫球蛋白血清水平的动态变化。采用受试者工作特征(ROC)曲线和一致性指数(C指数)比较生存预测能力。
IRE后,CD4 T细胞、CD8 T细胞、NK细胞、IL-2、C3、C4和IgG先出现短暂下降,随后稳步上升,而调节性T细胞、IL-6和IL-10则呈现相反趋势。D3和D7之间CD8 T细胞的变化被确定为总生存期(OS)和无进展生存期(PFS)的预后因素。CD8 T细胞变化对OS和PFS的ROC曲线值(AUC)和C指数分别为0.816和0.773以及0.816和0.639,均大于其他基于免疫或炎症的指标。
本研究首次提供了LAPC患者基于IRE的免疫调节证据。D3和D7之间CD8 T细胞的变化表现相对良好,可作为IRE后LAPC患者预后评估的有效工具。