组织电阻降低与胰腺癌不可逆电穿孔治疗的适应性免疫反应和生存相关。

Tissue Resistance Decrease during Irreversible Electroporation of Pancreatic Cancer as a Biomarker for the Adaptive Immune Response and Survival.

机构信息

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers (UMC), location Vrije Universiteit, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands.

出版信息

J Vasc Interv Radiol. 2023 Oct;34(10):1777-1784.e4. doi: 10.1016/j.jvir.2023.06.027. Epub 2023 Jun 28.

DOI:10.1016/j.jvir.2023.06.027

PMID:37391072

Abstract

PURPOSE

To correlate irreversible electroporation (IRE) procedural resistance changes with survival outcomes and the IRE-induced systemic immune response in patients with locally advanced pancreatic cancer (LAPC).

MATERIALS AND METHODS

Data on IRE procedural tissue resistance (R) features and survival outcomes were collected from patients with LAPC treated within the context of 2 prospective clinical trials in a single tertiary center. Preprocedural and postprocedural peripheral blood samples were prospectively collected for immune monitoring. The change (ie, decrease) in R during the first 10 test pulses (ΔR) and during the total procedure (ΔR) were calculated. Patients were divided in 2 groups on the basis of the median change in R (large ΔR vs small ΔR) and compared for differences in overall survival (OS) and progression-free survival and immune cell subsets.

RESULTS

A total of 54 patients were included; of these, 20 underwent immune monitoring. Linear regression modeling showed that the first 10 test pulses reflected the change in tissue resistance during the total procedure appropriately (P < .001; R = 0.91). A large change in tissue resistance significantly correlated with a better OS (P = .026) and longer time to disease progression (P = .045). Furthermore, a large change in tissue resistance was associated with CD8 T cell activation through significant upregulation of Ki-67 (P = .02) and PD-1 (P = .047). Additionally, this subgroup demonstrated significantly increased expression of CD80 on conventional dendritic cells (cDC1; P = .027) and PD-L1 on immunosuppressive myeloid-derived suppressor cells (P = .039).

CONCLUSIONS

IRE procedural resistance changes may serve as a biomarker for survival and IRE-induced systemic CD8 T cell and cDC1 activation.

摘要

目的

在局部晚期胰腺癌（LAPC）患者中，将不可逆电穿孔（IRE）程序阻力变化与生存结果和 IRE 诱导的全身免疫反应相关联。

材料与方法

在单一的三级中心内，对接受 LAPC 治疗的患者进行了两项前瞻性临床试验，收集了有关 IRE 程序组织阻力（R）特征和生存结果的数据。前瞻性收集了预处理和后处理的外周血样本以进行免疫监测。计算了前 10 个测试脉冲期间（ΔR）和整个过程中（ΔR）的 R 变化（即减少）。根据 R 中位数变化（大ΔR 与小ΔR）将患者分为两组，并比较总生存期（OS）、无进展生存期和免疫细胞亚群的差异。

结果

共纳入 54 例患者，其中 20 例进行了免疫监测。线性回归模型表明，前 10 个测试脉冲恰当地反映了整个过程中组织阻力的变化（P<0.001；R=0.91）。组织阻力的较大变化与更好的 OS（P=0.026）和疾病进展时间更长（P=0.045）显著相关。此外，组织阻力的较大变化与 CD8 T 细胞的激活有关，通过 Ki-67（P=0.02）和 PD-1（P=0.047）的显著上调。此外，该亚组的传统树突状细胞（cDC1）上 CD80 的表达显著增加（P=0.027），免疫抑制性髓系来源抑制细胞（P=0.039）上 PD-L1 的表达增加。