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已发表论文
抗 CD24 抗体联合脂质体阿霉素治疗射频消融不完全后的残留癌
Authors Liu J, Sun B, Li J , Liu X, Zhang G, Lei Z, Zheng C, Kan X
Received 29 May 2025
Accepted for publication 6 September 2025
Published 18 September 2025 Volume 2025:14 Pages 1053—1071
DOI https://doi.org/10.2147/ITT.S539926
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Flavio Salazar-Onfray
Jiayun Liu,1– 3,* Bo Sun,1– 3,* Jing Li,1– 3,* Xiaocui Liu,1– 3 Guilin Zhang,1– 3 Ziqiao Lei,1– 3 Chuansheng Zheng,1– 3 Xuefeng Kan1– 3
1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, 430022, People’s Republic of China; 3Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xuefeng Kan, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email xkliulang1314@163.com Chuansheng Zheng, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email hqzcsxh@sina.com
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.
Keywords: radiofrequency ablation, hepatocellular carcinoma, residual tumors, cd24 protein, liposomal doxorubicin
1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, 430022, People’s Republic of China; 3Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xuefeng Kan, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email xkliulang1314@163.com Chuansheng Zheng, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email hqzcsxh@sina.com
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.
Keywords: radiofrequency ablation, hepatocellular carcinoma, residual tumors, cd24 protein, liposomal doxorubicin