抗cd24抗体加阿霉素脂质体治疗不完全射频消融后残留肿瘤。

IF 4.4 Q1 IMMUNOLOGY
ImmunoTargets and Therapy Pub Date : 2025-09-18 eCollection Date: 2025-01-01 DOI:10.2147/ITT.S539926
Jiayun Liu, Bo Sun, Jing Li, Xiaocui Liu, Guilin Zhang, Ziqiao Lei, Chuansheng Zheng, Xuefeng Kan
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引用次数: 0

摘要

背景:对大尺寸或高危部位的实体恶性肿瘤进行完全射频消融(RFA)是具有挑战性的。阿霉素脂质体(L-Dox)在实体瘤中缓慢释放阿霉素,可选择性地抑制免疫抑制细胞。本研究探讨了利用抗cd24抗体联合L-Dox抑制肝细胞癌(HCC)不完全射频消融(iRFA)后残留癌的可行性,试图降低RFA后肿瘤复发率。方法:检测人肝癌细胞iRFA后残余癌组织中CD24蛋白和唾液酸结合样凝集素10 (siglece -10)的表达。采用(1)伪iRFA治疗小鼠原位肝癌模型:将消融电极仅置于活体肿瘤中,不进行消融治疗;(2) iRFA:肿瘤只接受iRFA治疗;(3) iRFA+抗cd24抗体;(4)承担+ L-Dox;(5) iRFA+抗cd24抗体+L-Dox。评估比较各组治疗后肿瘤的治疗效果及免疫微环境。结果:CD24蛋白和siglece -10在残癌pp+T细胞中高表达。结论:抗cd24抗体联合L-Dox治疗可显著改善肿瘤抑制性免疫微环境,使残留癌具有较强的肿瘤杀伤免疫,显著抑制肝癌iRFA后残留癌的发生。这些发现可能会为提高RFA治疗大型HCC或高危部位HCC的疗效提供新的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anti-CD24 Antibody Plus Liposomal Doxorubicin for the Management of Residual Cancers After Incomplete Radiofrequency Ablation.

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.

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来源期刊
CiteScore
16.50
自引率
0.00%
发文量
7
审稿时长
16 weeks
期刊介绍: Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.
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