为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons.
Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons.
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肝移植(LT)已成为肝细胞癌(HCC)的治愈性策略,但在免疫抑制背景下,其导致HCC复发的倾向更高,尤其是对于超出Milan标准的肿瘤。尽管免疫治疗已显著改善了免疫功能正常患者的生存期,并已成为包括HCC在内的多种肿瘤的标准治疗,但由于可能致命的同种异体移植物排斥反应,其主要用于器官移植范围之外。
然而,越来越多的证据拓展了HCC免疫治疗的治疗范式,从移植前的降期或桥接管理,到移植后的挽救或辅助策略。一般来说,免疫治疗主要包括免疫检查点抑制剂(ICIs)、过继细胞转移(ACT)和疫苗治疗。在LT中,ICIs以及随后的ACT研究最为深入,并取得了一些有希望的结果。由于免疫抑制剂与免疫治疗联合时复杂的肿瘤微环境和免疫反应性,难以就免疫抑制剂调整方案以及免疫治疗和患者的最佳选择达成共识。
此外,缺乏用于识别排斥反应和肿瘤反应的有效生物标志物,仍然是LT临床免疫治疗成功应用未解决的障碍。在这篇综述中,我们全面总结了针对HCC的LT中免疫治疗应用的现有证据。
此外,我们讨论了关于移植物保护和抗肿瘤反应同时实现这一目标的临床关注问题。
Liver transplantation (LT) has emerged as a curative strategy for hepatocellular carcinoma (HCC), but contributes to a higher predisposition to HCC recurrence in the immunosuppression context, especially for tumors beyond the Milan criteria. Although immunotherapy has dramatically improved survival for immunocompetent patients and has become the standard of care for a variety of tumors, including HCC, it is mainly used outside the scope of organ transplantation owing to potentially fatal allograft rejection.
Nevertheless, accumulative evidence has expanded the therapeutic paradigms of immunotherapy for HCC, from downstaging or bridging management in the pretransplant setting to the salvage or adjuvant strategy in the posttransplant setting. Generally, immunotherapy mainly includes immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT) and vaccine therapy.
ICIs, followed by ACT, have been most investigated in LT, with some promising results. Because of the complex tumor microenvironment and immunoreactivity when immunosuppressants are combined with immunotherapy, it is difficult to reach formulations for immunosuppressant adjustment and the optimal selection of immunotherapy as well as patients.
In addition, the absence of effective biomarkers for identifying rejection and tumor response is still an unresolved barrier to successful clinical immunotherapy applications for LT. In this review, we comprehensively summarize the available evidence of immunotherapy used in LT that is specific to HCC.
Moreover, we discuss clinically concerning issues regarding the concurrent goals of graft protection and antitumor response.
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