Abstract
BACKGROUND: Achieving a complete radiofrequency ablation (RFA) for a solid malignant tumor of large size or at high-risk locations is challenging. A slow release of doxorubicin by liposomal doxorubicin (L-Dox) in solid tumors can selectively suppress the immune suppressive cells. In this study, the feasibility of using anti-CD24 antibody plus L-Dox was explored to inhibit residual cancers after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC), with an attempt to reduce the tumor recurrences post-RFA. METHODS: The expressions of CD24 protein and sialic-acid-binding lg-like lectin 10 (Siglec-10) in residual cancers after iRFA of human HCC were evaluated. The mice orthotopic HCC models were treated by (1) pseudo iRFA: the ablation electrode was only put in the live tumor but without ablation treatment; (2) iRFA: the tumors only received iRFA treatment; (3) iRFA+anti-CD24 antibody; (4) iRFA+L-Dox; (5) iRFA+anti-CD24 antibody+L-Dox. The treatment effects and the immune microenvironment of treated tumors in each group were assessed and compared. RESULTS: The CD24 protein and Siglec-10 were highly expressed in the residual cancers (p<0.001). The iRFA+anti-CD24 antibody+L-Dox group had the smallest tumor size and the longest survival time (p<0.001). The anti-CD24 antibody in combination with L-Dox significantly decreased the expressions of CD24 and Siglec-10, significantly promoted the polarization of M2-like tumor-associated macrophages (TAMs) towards M1-like TAMs, significantly reduced the regulatory T cells and myeloid-derived suppressor cells, and significantly increased the infiltrations of natural killer cells and functional CD8(+)T cells into residual cancers. CONCLUSION: The combined therapy of anti-CD24 antibody with L-Dox could significantly improve the suppressive tumor immune microenvironment and result in a strong tumor-killing immunity in residual cancers, which significantly inhibited the residual cancers after iRFA of HCC. These findings may lead to a new strategy of enhancing the curative efficacy of RFA for large-sized HCC or HCC at high-risk locations.