SIR 2024
Interventional Oncology
Bo Yu, PhD
Research Assistant Professor
Northwestern University Feinberg School of Medicine
Disclosure information not submitted.
Robert Lewandowski, MD, FSIR
Professor
Northwestern University
Financial relationships: Full list of relationships is listed on the CME information page.
Dong-Hyun Kim, PhD (he/him/his)
Associate Professor
Northwestern University/Department of Radiology
Financial relationships: Full list of relationships is listed on the CME information page.
Immuno-ethanol ablation using an ethanol and immune adjuvant formulation is investigated as a potent anti-cancer immuno-ablative approach which can achieve a synergistic anticancer effect in the treatment of hepatocellular carcinoma (HCC).
Materials and Methods:
Ethanol concentration- and exposure time-dependent cancer cellular responses were characterized. Water insoluble anti-cancer/anti-inflammatory Curcumin was combined with ethanol as an immuno-ablation agent. Cellular uptake efficiency of Curcumin, cancer cell killing effect, and inflammatory marker changes (STAT3, p65, PD-L1, and GPX-4) of ethanol-curcumin treatment were characterized with confocal fluorescent microscope, CCK8, and Western blot assay. To evaluate the potential in vivo anti-cancer immunity of ethanol-curcumin treatment, the right lobe of rat liver and left lobe of rat liver were simultaneously inoculated N1S1 HCC cells (5 million) and a mixture of treated N1S1 cells (2.5 million, 10% ethanol only or 10% ethanol-curcumin) respectively in Sprague Dawley rats (n=15, each group: 5 rats, control: non-treated N1S1 HCC cell implantation). Tumor growth and immune response of each group were characterized with 7T MRI, flowcytometry analysis, and immunohistology.
Results:
Ethanol concentration gradient during the ethanol ablation treatment might induce an incomplete cancer cell death and inflammatory markers. Our optimized ethanol-curcumin treatment as a form of immuno-ethanol ablation contributed to an enhanced cellular uptake of Curcumin, increased cancer cell killing, and decreased inflammatory reaction. The ethanol-curcumin treated HCC cell implantation in the rat liver demonstrated anti-cancer immune mediated N1S1 HCC tumor rejection. The secondary tumor growth with simultaneously implanted non-treated N1S1 HCC cells in left lobe was also significantly suppressed with the tumor growth inhibition of ethanol-curcumin treated N1S1 HCC cells (P < 0.05). It is indicating a potential anti-cancer immunity mediated abscopal effect of ethanol-curcumin immuno-ablation. Significantly increased CD8 T cell infiltration and CD8/Treg ratio in the experimental group compared to the control confirmed the activated anti-cancer immunity (P < 0.01).
Conclusion:
Synergistic anti-cancer effect of immuno-ethanol ablation therapy could be achieved with ethanol-curcumin agent. The results underscore the importance of coherent immuno-ablation therapeutic procedures using optimized therapeutic agents for the synergistic therapeutic outcomes.