{"title":"阻断Tim-3可增强CD8+ T细胞活性,抑制射频消融后肝癌复发。","authors":"Na Wu, Xinru Pei, Weiguo Cai, Xiaodie Ye, Wei Lu","doi":"10.1080/02656736.2025.2516502","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Incomplete radiofrequency ablation (iRFA) for hepatocellular carcinoma (HCC) during radiofrequency ablation (RFA) may result in rapid progression of residual tumors and resistance to anti-PD-1 therapy. Research has demonstrated elevated T-cell immunoglobulin and mucin domain 3 (Tim-3) expression in CD8<sup>+</sup> T cells in the peripheral blood of patients with HCC after RFA, leading to a diminished anti-tumor immune response. Therefore, this study examined the effectiveness of anti-Tim-3 therapy in treating residual tumors after iRFA and explored the underlying mechanisms.</p><p><strong>Methods: </strong>To examine the expression of Tim-3 in the residual tumors after iRFA for HCC in mice. Treat residual tumors with anti-αTim-3 and evaluate its efficacy. Transcriptomic sequencing was conducted on the residual tumors to explore the underlying mechanisms. Meanwhile, residual tumors were treated with a combination of anti-αTim-3 and anti-αPD-1 to evaluate efficacy.</p><p><strong>Results: </strong>This study demonstrated elevated Tim-3 expression in CD8<sup>+</sup> T cells within residual tumors after iRFA. CD8<sup>+</sup> T cells exhibit attenuated anti-tumor immune responses associated with accelerated tumor progression. Treatment with anti-αTim-3 impeded the advancement of residual tumors by enhancing CD8<sup>+</sup> T cell infiltration and stimulating their anti-tumor activities. Furthermore, anti-αTim-3 therapy upregulated PD-1 expression in residual tumors. Combination therapy involving anti-αTim-3 and anti-αPD-1 elicited a robust anti-tumor immune response.</p><p><strong>Conclusions: </strong>Tim-3 expression is elevated in CD8<sup>+</sup> T cells within residual tumors after iRFA, which contributed to their accelerated advancement. Anti-αTim-3 slows tumor progression by boosting CD8<sup>+</sup> T cell anti-tumor activity and enhancing response to anti-αPD-1 treatment.</p>","PeriodicalId":520653,"journal":{"name":"International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group","volume":"42 1","pages":"2516502"},"PeriodicalIF":3.0000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Blocking Tim-3 enhances CD8<sup>+</sup> T cell activity to inhibit hepatocellular carcinoma recurrence post-radiofrequency ablation.\",\"authors\":\"Na Wu, Xinru Pei, Weiguo Cai, Xiaodie Ye, Wei Lu\",\"doi\":\"10.1080/02656736.2025.2516502\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Incomplete radiofrequency ablation (iRFA) for hepatocellular carcinoma (HCC) during radiofrequency ablation (RFA) may result in rapid progression of residual tumors and resistance to anti-PD-1 therapy. Research has demonstrated elevated T-cell immunoglobulin and mucin domain 3 (Tim-3) expression in CD8<sup>+</sup> T cells in the peripheral blood of patients with HCC after RFA, leading to a diminished anti-tumor immune response. Therefore, this study examined the effectiveness of anti-Tim-3 therapy in treating residual tumors after iRFA and explored the underlying mechanisms.</p><p><strong>Methods: </strong>To examine the expression of Tim-3 in the residual tumors after iRFA for HCC in mice. Treat residual tumors with anti-αTim-3 and evaluate its efficacy. Transcriptomic sequencing was conducted on the residual tumors to explore the underlying mechanisms. Meanwhile, residual tumors were treated with a combination of anti-αTim-3 and anti-αPD-1 to evaluate efficacy.</p><p><strong>Results: </strong>This study demonstrated elevated Tim-3 expression in CD8<sup>+</sup> T cells within residual tumors after iRFA. CD8<sup>+</sup> T cells exhibit attenuated anti-tumor immune responses associated with accelerated tumor progression. Treatment with anti-αTim-3 impeded the advancement of residual tumors by enhancing CD8<sup>+</sup> T cell infiltration and stimulating their anti-tumor activities. Furthermore, anti-αTim-3 therapy upregulated PD-1 expression in residual tumors. Combination therapy involving anti-αTim-3 and anti-αPD-1 elicited a robust anti-tumor immune response.</p><p><strong>Conclusions: </strong>Tim-3 expression is elevated in CD8<sup>+</sup> T cells within residual tumors after iRFA, which contributed to their accelerated advancement. Anti-αTim-3 slows tumor progression by boosting CD8<sup>+</sup> T cell anti-tumor activity and enhancing response to anti-αPD-1 treatment.</p>\",\"PeriodicalId\":520653,\"journal\":{\"name\":\"International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group\",\"volume\":\"42 1\",\"pages\":\"2516502\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/02656736.2025.2516502\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/02656736.2025.2516502","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/16 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
背景:在射频消融(RFA)过程中,不完全射频消融(iRFA)治疗肝细胞癌(HCC)可能导致残留肿瘤的快速进展和抗pd -1治疗的耐药。研究表明,RFA后HCC患者外周血CD8+ T细胞中T细胞免疫球蛋白和粘蛋白结构域3 (Tim-3)表达升高,导致抗肿瘤免疫反应减弱。因此,本研究考察了抗tim -3治疗iRFA后残留肿瘤的有效性,并探讨其潜在机制。方法:检测Tim-3在肝细胞癌iRFA后残余肿瘤中的表达。用抗α tim -3治疗残余肿瘤并评价其疗效。对残余肿瘤进行转录组测序以探索其潜在机制。同时,联合抗α tim -3和抗α pd -1治疗残余肿瘤,评价疗效。结果:本研究表明,iRFA后残余肿瘤内CD8+ T细胞中Tim-3表达升高。CD8+ T细胞表现出与肿瘤加速进展相关的抗肿瘤免疫反应减弱。抗α tim -3治疗通过增强CD8+ T细胞浸润,刺激其抗肿瘤活性,从而抑制残余肿瘤的进展。此外,抗α tim -3治疗可上调残余肿瘤中PD-1的表达。抗α tim -3和抗α pd -1联合治疗可引起强大的抗肿瘤免疫反应。结论:iRFA后残余肿瘤内CD8+ T细胞Tim-3表达升高,加速肿瘤进展。抗α tim -3通过提高CD8+ T细胞抗肿瘤活性和增强抗α pd -1治疗的应答来减缓肿瘤进展。
Blocking Tim-3 enhances CD8+ T cell activity to inhibit hepatocellular carcinoma recurrence post-radiofrequency ablation.
Background: Incomplete radiofrequency ablation (iRFA) for hepatocellular carcinoma (HCC) during radiofrequency ablation (RFA) may result in rapid progression of residual tumors and resistance to anti-PD-1 therapy. Research has demonstrated elevated T-cell immunoglobulin and mucin domain 3 (Tim-3) expression in CD8+ T cells in the peripheral blood of patients with HCC after RFA, leading to a diminished anti-tumor immune response. Therefore, this study examined the effectiveness of anti-Tim-3 therapy in treating residual tumors after iRFA and explored the underlying mechanisms.
Methods: To examine the expression of Tim-3 in the residual tumors after iRFA for HCC in mice. Treat residual tumors with anti-αTim-3 and evaluate its efficacy. Transcriptomic sequencing was conducted on the residual tumors to explore the underlying mechanisms. Meanwhile, residual tumors were treated with a combination of anti-αTim-3 and anti-αPD-1 to evaluate efficacy.
Results: This study demonstrated elevated Tim-3 expression in CD8+ T cells within residual tumors after iRFA. CD8+ T cells exhibit attenuated anti-tumor immune responses associated with accelerated tumor progression. Treatment with anti-αTim-3 impeded the advancement of residual tumors by enhancing CD8+ T cell infiltration and stimulating their anti-tumor activities. Furthermore, anti-αTim-3 therapy upregulated PD-1 expression in residual tumors. Combination therapy involving anti-αTim-3 and anti-αPD-1 elicited a robust anti-tumor immune response.
Conclusions: Tim-3 expression is elevated in CD8+ T cells within residual tumors after iRFA, which contributed to their accelerated advancement. Anti-αTim-3 slows tumor progression by boosting CD8+ T cell anti-tumor activity and enhancing response to anti-αPD-1 treatment.