Hepatic Arterial Bland Embolization Increases Th17 Cell Infiltration in a Syngeneic Rat Model of Hepatocellular Carcinoma

Rony Avritscher, Na Hyun Jo, Urszula Polak, Andrea C. Cortes, Hideyuki Nishiofuku, Bruno C. Odisio, Haruyuki Takaki, Alda L. Tam, Marites P. Melancon, Steven Yevich, Aliya Qayyum, Ahmed Kaseb, Kimihiko Kichikawa, Sanjay Gupta, S. Nahum Goldberg, Seon Hee Chang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose: To determine the tumor immune cell landscape after transcatheter arterial bland embolization (TAE) in a clinically relevant rat hepatocellular carcinoma (HCC) model. Materials and Methods: Buffalo rats (n = 21) bearing syngeneic McArdle RH-7777 rat hepatoma cells implanted into the left hepatic lobe underwent TAE using 70–150 µm beads (n = 9) or hepatic artery saline infusion (n = 12). HCC nodules, peritumoral margin, adjacent non-cancerous liver, and splenic parenchyma were collected and disaggregated to generate single-cell suspensions for immunological characterization 14 d after treatment. Changes in tumor-infiltrating immune subsets including CD4 T cells (Th17 and Treg), CD8 cytotoxic T cells (IFNγ), and neutrophils were evaluated by multiparameter flow cytometry. Migration and colony formation assays were performed to examine the effect of IL-17, a signature cytokine of Th17 cells, on McArdle RH-7777 hepatoma cells under conditions simulating post-embolization environment (i.e., hypoxia and nutrient privation). Statistical significance was determined by the Student unpaired t test or one-way ANOVA. Results: TAE induces increased infiltration of Th17 cells in liver tumors when compared with controls 14 d after treatment (0.29 ± 0.01 vs. 0.19 ± 0.02; p = 0.02). A similar pattern was observed in the spleen (1.41 ± 0.13 vs. 0.57 ± 0.08; p < 0.001), indicating both local and systemic effect. No significant differences in the percentage of FoxP3 + Tregs, IFNγ-producing CD4 T cells, and CD8 T cells were observed between groups (p > 0.05). In vitro post-embolization assays demonstrated that IL-17 reduces McA-RH7777 cell migration at 24–48 h (p = 0.003 and p = 0.002, respectively). Conclusion: Transcatheter hepatic arterial bland embolization induces local and systemic increased infiltration of Th17 cells and expression of their signature cytokine IL-17. In a simulated post-embolization environment, IL-17 significantly reduced McA-RH7777 cell migration.

Original languageEnglish (US)
Pages (from-to)311-321
Number of pages11
JournalCardiovascular and Interventional Radiology
Volume43
Issue number2
DOIs
StatePublished - Feb 1 2020

Keywords

  • HCC immune landscape
  • IL-17
  • Th17 cells
  • Transcatheter hepatic arterial bland embolization
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Hepatic Arterial Bland Embolization Increases Th17 Cell Infiltration in a Syngeneic Rat Model of Hepatocellular Carcinoma'. Together they form a unique fingerprint.

Cite this