{
  "abstract": "Background Nanosecond pulsed electric field (nsPEF) ablation has demonstrated limited and transient efficacy in suppressing tumor progression. Oncolytic peptide LTX-315 is known to elicit a strong antitumor immune response and durable immune memory. This study aimed to investigate whether LTX-315 could enhance nsPEF-induced antitumor immunity in liver cancer.Methods Both cell assays and mouse models were used to evaluate the therapeutic efficacy of nsPEF, LTX-315, and combination therapy. Flow cytometry and immunofluorescence were performed to assess the tumor immune microenvironment. Co-culture models were established to evaluate the functional modulation of immune cells.Results nsPEF upregulated the programmed cell death 1 ligand 1 (PD-L1) expression in liver cancer cells, leading to CD8 + T-cell dysfunction. LTX-315 reduced the nsPEF-mediated elevated PD-L1 level and restored the cytotoxicity of CD8+ T cells. Furthermore, LTX-315 acted with nsPEF to induce enhanced immunogenic cell death for the activation of dendritic cells and CD8+ T cells. In addition, LTX-315 improved antigen processing and presentation in nsPEF-treated liver cancer cells. Notably, the combination of nsPEF and LTX-315 achieved durable tumor control and prolonged survival of the tumor-bearing mice, by promoting the migration of dendritic cells to tumor-draining lymph nodes, the infiltration of immune cells within the tumor and potential immune memory to prevent tumor metastasis.Conclusions LTX-315 functions as an immune stimulant to improve the antitumor efficacy of nsPEF. The combination of nsPEF and LTX-315 represents a promising interventional immunotherapy strategy for liver cancer.Key points LTX-315; Antitumor immune response; nsPEF; Liver cancer.",
  "authors": [
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital,Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"
      ],
      "name": "Kun Ji"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital,Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"
      ],
      "name": "Li Jing"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital,Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"
      ],
      "name": "Tiantian Xu"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital,Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"
      ],
      "name": "Shoujin Cao"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Cong Zhang"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Zilin Wang"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital,Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"
      ],
      "name": "Guanhui Zhou"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Yunbo Cao"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Jiahua Niu"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Yuning Yang"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Xinhua Chen"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Jing Ai"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital,Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"
      ],
      "name": "Jun-Hui Sun"
    },
    {
      "affiliations": [
        "Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital,Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China"
      ],
      "name": "Bin Xiong"
    }
  ],
  "title": "Oncolytic peptide LTX-315 targets PD-L1 to improve antitumor immune response of nanosecond pulse electric field in liver cancer",
  "uid": "a996e716-a652-5c2e-a1cc-ec3ab36a4cfc"
}