Comparative Analysis of Immunoactivation by Nanosecond Pulsed Electric Fields and PD-1 Blockade in Murine Hepatocellular Carcinoma

Nanosecond pulsed electric field (NsPEF) ablation effectively eliminates early-stage hepatocellular carcinoma (HCC) by local ablation and advanced HCC by inducing a remarkable and sustained host immune response. However, this approach is not sufficient to prevent cancer progression, and complementar...

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Main Authors: Maiweilidan Yimingjiang, Talaiti Tuergan, Xinhua Chen, Hao Wen, Yingmei Shao, RuiQing Zhang, Kasimu Aihaiti, Jing Xue, Tuerganaili Aji, Wei Zhang
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Analytical Cellular Pathology
Online Access:http://dx.doi.org/10.1155/2020/9582731
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author Maiweilidan Yimingjiang
Talaiti Tuergan
Xinhua Chen
Hao Wen
Yingmei Shao
RuiQing Zhang
Kasimu Aihaiti
Jing Xue
Tuerganaili Aji
Wei Zhang
author_facet Maiweilidan Yimingjiang
Talaiti Tuergan
Xinhua Chen
Hao Wen
Yingmei Shao
RuiQing Zhang
Kasimu Aihaiti
Jing Xue
Tuerganaili Aji
Wei Zhang
author_sort Maiweilidan Yimingjiang
collection DOAJ
description Nanosecond pulsed electric field (NsPEF) ablation effectively eliminates early-stage hepatocellular carcinoma (HCC) by local ablation and advanced HCC by inducing a remarkable and sustained host immune response. However, this approach is not sufficient to prevent cancer progression, and complementary approaches are necessary for effective immunotherapy. In this study, we evaluated the immunoactivating effects and mechanisms of action of nsPEF ablation and PD-1 blockade on an HCC orthotopic xenograft mouse model. Briefly, 24 C57BL-6J tumor-bearing mice were randomly assigned to three groups: nsPEF ablation group, anti-PD-1 administration group, and untreated control group. Tumor-infiltrating T, B, and NK cell levels and plasma concentrations of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-5, IL-6, and IL-10), Th9 (IL-9), and Th17 (IL-17A, IL-17F, IL-21, and IL-22) cytokines were evaluated. Both nsPEF ablation and anti-PD-1 treatment induced immune cell infiltration in local tumors and modulated cytokine levels in the peripheral blood, with distinct changes in the two treatment groups. Based on these findings, both nsPEF ablation and PD-1 antibody administration can trigger a local and systemic immune response in a partially complementary manner, and nsPEF ablation should be considered along with PD-1 blockade for the treatment of HCC.
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spelling doaj-art-f26b8ba856e44294a2408780b8a6b0332025-02-03T05:53:52ZengWileyAnalytical Cellular Pathology2210-71772210-71852020-01-01202010.1155/2020/95827319582731Comparative Analysis of Immunoactivation by Nanosecond Pulsed Electric Fields and PD-1 Blockade in Murine Hepatocellular CarcinomaMaiweilidan Yimingjiang0Talaiti Tuergan1Xinhua Chen2Hao Wen3Yingmei Shao4RuiQing Zhang5Kasimu Aihaiti6Jing Xue7Tuerganaili Aji8Wei Zhang9Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, ChinaDepartment of Hepatic Hydatid and Hepatobiliary Surgery, Digestive and Vascular Surgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, ChinaCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, ChinaState Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, ChinaDepartment of Hepatic Hydatid and Hepatobiliary Surgery, Digestive and Vascular Surgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, ChinaDepartment of Hepatic Hydatid and Hepatobiliary Surgery, Digestive and Vascular Surgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, ChinaDepartment of Hepatic Hydatid and Hepatobiliary Surgery, Digestive and Vascular Surgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, ChinaXinjiang Medical University, Urumqi, Xinjiang 830011, ChinaDepartment of Hepatic Hydatid and Hepatobiliary Surgery, Digestive and Vascular Surgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, ChinaDepartment of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, ChinaNanosecond pulsed electric field (NsPEF) ablation effectively eliminates early-stage hepatocellular carcinoma (HCC) by local ablation and advanced HCC by inducing a remarkable and sustained host immune response. However, this approach is not sufficient to prevent cancer progression, and complementary approaches are necessary for effective immunotherapy. In this study, we evaluated the immunoactivating effects and mechanisms of action of nsPEF ablation and PD-1 blockade on an HCC orthotopic xenograft mouse model. Briefly, 24 C57BL-6J tumor-bearing mice were randomly assigned to three groups: nsPEF ablation group, anti-PD-1 administration group, and untreated control group. Tumor-infiltrating T, B, and NK cell levels and plasma concentrations of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-5, IL-6, and IL-10), Th9 (IL-9), and Th17 (IL-17A, IL-17F, IL-21, and IL-22) cytokines were evaluated. Both nsPEF ablation and anti-PD-1 treatment induced immune cell infiltration in local tumors and modulated cytokine levels in the peripheral blood, with distinct changes in the two treatment groups. Based on these findings, both nsPEF ablation and PD-1 antibody administration can trigger a local and systemic immune response in a partially complementary manner, and nsPEF ablation should be considered along with PD-1 blockade for the treatment of HCC.http://dx.doi.org/10.1155/2020/9582731
spellingShingle Maiweilidan Yimingjiang
Talaiti Tuergan
Xinhua Chen
Hao Wen
Yingmei Shao
RuiQing Zhang
Kasimu Aihaiti
Jing Xue
Tuerganaili Aji
Wei Zhang
Comparative Analysis of Immunoactivation by Nanosecond Pulsed Electric Fields and PD-1 Blockade in Murine Hepatocellular Carcinoma
Analytical Cellular Pathology
title Comparative Analysis of Immunoactivation by Nanosecond Pulsed Electric Fields and PD-1 Blockade in Murine Hepatocellular Carcinoma
title_full Comparative Analysis of Immunoactivation by Nanosecond Pulsed Electric Fields and PD-1 Blockade in Murine Hepatocellular Carcinoma
title_fullStr Comparative Analysis of Immunoactivation by Nanosecond Pulsed Electric Fields and PD-1 Blockade in Murine Hepatocellular Carcinoma
title_full_unstemmed Comparative Analysis of Immunoactivation by Nanosecond Pulsed Electric Fields and PD-1 Blockade in Murine Hepatocellular Carcinoma
title_short Comparative Analysis of Immunoactivation by Nanosecond Pulsed Electric Fields and PD-1 Blockade in Murine Hepatocellular Carcinoma
title_sort comparative analysis of immunoactivation by nanosecond pulsed electric fields and pd 1 blockade in murine hepatocellular carcinoma
url http://dx.doi.org/10.1155/2020/9582731
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