Combined use of microwave ablation and cell immunotherapy induces nonspecific immunity of hepatocellular carcinoma model mice

Cell Cycle. 2020 Dec;19(24):3595-3607. doi: 10.1080/15384101.2020.1853942. Epub 2020 Dec 7.

Abstract

Microwave ablation (MWA) has been widely used in the treatment of solid tumors. Studies have been less conducted on the efficacy of MWA used with cell immunotherapy in treating hepatocellular carcinoma (HCC). The current study aimed at exploring the efficacy of MWA in combination with cell immunotherapy in treating HCC. Hepa1-6 HCC mice were treated by MWA, blockade, or the combined therapy (MWA used with blockade), or left untreated. Survival rates of the mice were plotted by Kaplan-Meier Curve, followed by log-rank test. 25 days after the operation, surviving mice were monitored for tumor recurrence, and tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were performed to detect the numbers of CD4+ and CD8+ cells in the tumors and spleens of mice. The expressions of related cytokines were detected and measured by ELISPOT and ELISA. The results showed that MWA combined with anti-PD-1/anti-CTLA-4 not only increased the survival time, protected the mice against tumor recurrence, but also enhanced the intratumoral infiltration of cytotoxic T lymphocyte and systemic T-cell immune responses induced by MWA through activation of synergistically specific antitumor immunity. In addition, the combined therapy increased T-helper 1 cell (Th1-type) cytokines, but reduced Th2-type cytokines, resulting in the polarization of Th1 cells. T-cell immune responses of HCC cells were activated by MWA. In addition, the combined therapy of MWA and anti-PD-1/anti-CTLA-4 induced Th1-type immune response, and showed specific antitumor immunity.

Keywords: Microwave ablation; cell immunotherapy; combination therapy; hepatocellular carcinoma; nonspecific immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CTLA-4 Antigen / antagonists & inhibitors
  • Carcinoma, Hepatocellular / mortality*
  • Carcinoma, Hepatocellular / therapy*
  • Combined Modality Therapy / methods
  • Cytokines / metabolism
  • Disease Models, Animal
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunity / radiation effects*
  • Immunotherapy / methods*
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microwaves / therapeutic use*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Radiofrequency Therapy / methods*
  • Signal Transduction / drug effects
  • Survival Rate
  • T-Lymphocytes, Cytotoxic / immunology
  • Th1 Cells / immunology
  • Treatment Outcome
  • Tumor Burden / radiation effects

Substances

  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Cytokines
  • Immune Checkpoint Inhibitors
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor

Grants and funding

This work was supported by the National Natural Science Foundation of China [81401494].