Characterizing the Anti-Tumor Immune Response to IRE vs Thermal Ablation Therapy in an Immunocompetent Oncopig Model of Hepatocellular Carcinoma

Tuesday, March 7, 2023

3:54 PM – 4:03 PM

Location: Phoenix Convention Center, 221AB

Presenting Author(s)

Justin Lee, BA

MD-PhD Candidate
UCLA-Caltech

Disclosure(s): No financial relationships to disclose

Author/Co-author(s)

Edward E. Boas, MD, PhD

Physician
City of Hope
MC

Monica Cappelletti, PhD

Adjunct Assistnat Professor, Pathology and Laboratory Medicine
UCLA
David S. Lu, MD (he/him/his)

Professor of Radiology, and Surgery
David Geffen School of Medicine at UCLA
Steven Raman, MD, FSAR, FSIR

Professor of Radiology, Urology and Surgery
David Geffen School of Medicine At UCLA
EL

Edward W. Lee, MD

Associate Professor
University of California, Los Angeles
JC

Jason Chiang, MD, PhD

Assistant Professor
Interventional Radiology, UCLA

Disclosure(s):

Justin Lee, BA: No financial relationships to disclose

David S. Lu, MD: Ethicon J&J: Advisory Committee or Review Panel Member (Ongoing), Consultant (Ongoing), Speaking and Teaching (Ongoing)

Purpose: Immunotherapies for cancer treatment are designed to mobilize a patient’s own immune system against their malignancy locally and systemically. Percutaneous ablation techniques have the potential to work in conjunction with modern immunotherapies by priming the patient’s own lymphocytes to attack previously untreated cancer cells. This phenomenon, known as the abscopal effect, has garnered interest because of the potential for locoregional therapies to induce local and systemic anti-tumor effects and shrinkage of distant tumors (Fionda, 2020). The goal of this study is to evaluate the anti-tumor immune response to irreversible electroporation (IRE) compared to microwave (MWA) and cryoablation in an immunocompetent Oncopig liver tumor model of hepatocellular carcinoma.

Materials and Methods: In-situ liver tumors were induced in a transgenic immunocompetent porcine liver model (2-4 tumors in each liver) with Cre-recombinase induced TP53 and KRAS mutations (Oncopig). Oncopigs were separated into three treatment groups (n=2), each undergoing either MWA, cryoablation or IRE treatment of a single liver tumor under US or CT guidance. Pre-, immediate post- and 1-week post ablation imaging was performed to evaluate treated and non-treated tumor growth. At each time point, venous blood was also drawn and assayed for critical cytokines related to anti- or pro-tumor immune response. Systemic cytokine levels were correlated to targeted and off-targeted tumor volumes after each time point.

Results:

Liver tumors were induced at an 83.3% (20/24) success rate. Treated tumors decreased by an average 7% in volume across all treatment modalities on 1-week follow-up imaging. Off-target tumors increased by volume by 71.7% with IRE, 13.6% with MWA and 1.4% with cryoablation. On 1-week blood samples, IRE treated pigs demonstrated lower circulating concentrations of pro-inflammatory IL-2 cytokines when compared to cryoablation (10.9 vs 40.7 pg/mL; p=0.051). There was no difference in IL-2 levels between MWA and cryoablation-treated pigs (40.7 vs 42.4 pg/mL; p=0.97).

Conclusion:

The pro- and anti-tumor immune response is dependent on the type of ablation modality. IRE had the lowest levels of inflammatory marker IL-2 and the lowest degree of tumor control in off target tumors at the one-week time point. Modulating inflammatory pathways via these cytokines after IRE may potentially play a role in amplifying the abscopal effect in liver tumors.