Abstract
Transarterial chemoembolization and transarterial embolization (TAE) induce tumor necrosis and expose the immune system to tumor debris with a demonstrated potential for immune activation; however, there remains limited data regarding differences in the immune response to different embolic agents. The goal of this study was to characterize the local immune response adjacent to two different embolics commonly used in the clinic. TAE was performed in a translational rat model (n = 20) of DEN-induced autochthonous HCC using either 40-120 um tris-acryl gelatin microspheres (TAGM) - Embosphere Microspheres (Merit Medical Systems) or 70-150 um polyvinyl alcohol 2-acrylamido-2-methylpropanesulfonate sodium salt (PVA-AMPS) - DC Bead LUMI (Biocompatibles Ltd). After embolization, paraffin embedded tumors were processed for Hematoxylin and Eosin (H&E) and immunohistochemical (IHC) staining with anti-CD3, anti-CD8a and anti-FoxP3. H&E samples were analyzed by an attending pathologist. Quantitation of immune cell populations on IHC was performed using BZ-X Analyzer (Keyence corp. Osaka, Japan). Data are reported as means and standard deviations with statistical comparisons made using a student’s t-test. H&E analysis demonstrated a foreign body reaction adjacent to TAGM that was nearly or fully absent when using PVA-AMPS beads. IHC staining revealed a quantitative difference in the number of Tumor Infiltrating Lymphocytes (TILs) around the beads. This difference was present in CD3+ T-cells (7.06 ± 5.1 vs. 3.16 ± 3.9, N = 36 and 19 respectively, P <0.005), CD8+ T-cells (5.71 ± 4.0 vs. 2.05 ± 1.9, N = 35 and 21 respectively, P <0.0005), and FoxP3+ve cells (3.15 ± 2.7 vs. 1.14 ± 1.7, N = 34 and 21 respectively, P <0.005). Additionally, TAGM beads demonstrated a bead dependent increase in the number of CD3 (P <0.005) and CD8 (P <0.005) infiltrating cells while PVA-AMPS did not. Embolization using TAGM demonstrated a prominent foreign body reaction adjacent to embolics in embolized tumors, associated with an increase in CD3+, CD8+ and FoxP3+ T-cells as compared to embolization performed with PVA-AMPS. Further studies are required to understand the underlying mechanism and therapeutic implications.
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