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CardioVascular and Interventional Radiology

, Volume 43, Issue 2, pp 311–321 | Cite as

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

  • Rony AvritscherEmail author
  • NaHyun 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
Laboratory Investigation Interventional Oncology
  • 268 Downloads
Part of the following topical collections:
  1. Interventional Oncology

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.

Keywords

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

Notes

Funding

This research was supported by BTG and SIO Immuno-Oncology-Interventional Oncology grant program, Biocompatibles UK Ltd (BTG), Surrey, UK, Grant# BTG-SP-08.004-F01, Sister Institution Network Fund (SINF) Grant# SINF-600801-80-115693-21, Department of Defense W81XWH-16-1-0100, and The University of Texas MD Anderson Cancer Center, and Center for Inflammation and Cancer Support Grant. The funders had no role in study design, data collection, analysis, interpretation of the data, decision to submit results, the decision to publish, or preparation of the manuscript.

Compliance with Ethical Standard

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

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Supplementary material 1 (TIFF 11514 kb)
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Supplementary material 2 (TIFF 3676 kb)
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Supplementary material 3 (DOCX 48 kb)
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Supplementary material 4 (DOCX 47 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2019

Authors and Affiliations

  • Rony Avritscher
    • 1
    Email author
  • NaHyun Jo
    • 1
  • Urszula Polak
    • 1
  • Andrea C. Cortes
    • 1
  • Hideyuki Nishiofuku
    • 2
  • Bruno C. Odisio
    • 1
  • Haruyuki Takaki
    • 3
  • Alda L. Tam
    • 1
  • Marites P. Melancon
    • 1
  • Steven Yevich
    • 1
  • Aliya Qayyum
    • 4
  • Ahmed Kaseb
    • 5
  • Kimihiko Kichikawa
    • 2
  • Sanjay Gupta
    • 1
  • S. Nahum Goldberg
    • 6
    • 7
  • Seon Hee Chang
    • 8
  1. 1.Department of Interventional RadiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of RadiologyIVR Center, Nara Medical UniversityKashiharaJapan
  3. 3.Department of Radiological TechnologyHyogo College of Medicine College HospitalNishinomiyaJapan
  4. 4.Department of Diagnostic RadiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA
  7. 7.Department of RadiologyHadassah Hebrew University Medical CenterJerusalemIsrael
  8. 8.Department of ImmunologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

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