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

  • Laboratory Investigation
  • Interventional Oncology
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

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.

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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.

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Authors and Affiliations

  1. Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Rony Avritscher, NaHyun Jo, Urszula Polak, Andrea C. Cortes, Bruno C. Odisio, Alda L. Tam, Marites P. Melancon, Steven Yevich & Sanjay Gupta

  2. Department of Radiology, IVR Center, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan

    Hideyuki Nishiofuku & Kimihiko Kichikawa

  3. Department of Radiological Technology, Hyogo College of Medicine College Hospital, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Hyogo, Japan

    Haruyuki Takaki

  4. Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Aliya Qayyum

  5. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Ahmed Kaseb

  6. Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA

    S. Nahum Goldberg

  7. Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel

    S. Nahum Goldberg

  8. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA

    Seon Hee Chang

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  1. Rony Avritscher
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Avritscher, R., Jo, N., Polak, U. et al. Hepatic Arterial Bland Embolization Increases Th17 Cell Infiltration in a Syngeneic Rat Model of Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 43, 311–321 (2020). https://doi.org/10.1007/s00270-019-02343-1

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