The Current Landscape of Immune Checkpoint Blockade in Hepatocellular Carcinoma: A Review.
The Current Landscape of Immune Checkpoint Blockade in Hepatocellular Carcinoma: A Review.
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DOI：
10.1001/jamaoncol.2020.3381
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发表时间：
2021-01-01
期刊：
影响因子：
28.4
通讯作者：
Duda DG
中科院分区：
文献类型：
--
作者：
Pinter M;Jain RK;Duda DG
十多年来，索拉非尼一直是晚期肝细胞癌（HCC）患者唯一的全身治疗选择。然而，过去几年的快速进展导致其他血管生成抑制剂和几种免疫检查点阻断剂（ICB）的批准，这些药物已被添加到晚期HCC的治疗药物中。此外，最近贝伐单抗与atezolizumab联合治疗的成功标志着HCC一线治疗的重要变化。本综述总结了在HCC中实施ICB的前景和挑战的快速出现的临床数据，并讨论了生物标志物预测治疗反应或耐药的未满足需求。还讨论了两种靶向肿瘤免疫抑制的策略：一种已被证实（血管内皮生长因子途径抑制），另一种正在研究中（转化生长因子-β途径抑制）。本文综述了ICB抑制HCC的原理和初步证据，以及ICB抑制HCC的免疫抑制环境和ICB增强HCC疗效的机制。血管生成抑制剂和ICB单独或联合使用的最新成功和失败为如何在HCC中实施这种新型全身治疗提供了重要见解，并为增强这种疾病的免疫治疗效果提供了新途径。
For more than a decade, sorafenib has been the only systemic treatment option for patients with advanced hepatocellular carcinoma (HCC). However, rapid progress over the past few years led to approval of other angiogenesis inhibitors and several immune checkpoint blockers (ICBs) that have been added to the treatment armamentarium for advanced HCC. Moreover, the recent success of a combination of bevacizumab with atezolizumab signals an important change in the front-line treatment of HCC. This review summarizes rapidly emerging clinical data on the promise and challenges of implementing ICBs in HCC and discusses the unmet need of biomarkers to predict response or resistance to therapy. Two strategies to target immunosuppression in tumors are also discussed: one proven (vascular endothelial growth factor pathway inhibition) and one currently under investigation (transforming growth factor-β pathway inhibition). The rationale and preliminary evidence on how their inhibition may reprogram the immunosuppressive milieu and enhance the efficacy of ICBs in HCC are reviewed. The recent successes and failures of angiogenesis inhibitors and ICBs, alone and in combination, have provided important insights into how to implement this novel systemic therapy in HCC and led to new avenues to enhance immunotherapy efficacy in this disease.
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分析肝细胞癌的基因组和转录组鉴定了转化生长因子-β途径中的突变和基因表达变化。
影响因子：
29.4
作者：
Chen J;Zaidi S;Rao S;Chen JS;Phan L;Farci P;Su X;Shetty K;White J;Zamboni F;Wu X;Rashid A;Pattabiraman N;Mazumder R;Horvath A;Wu RC;Li S;Xiao C;Deng CX;Wheeler DA;Mishra B;Akbani R;Mishra L
通讯作者：
Mishra L
影响因子：
4.6
作者：
Bonneville R;Krook MA;Kautto EA;Miya J;Wing MR;Chen HZ;Reeser JW;Yu L;Roychowdhury S
通讯作者：
Roychowdhury S
影响因子：
8
作者：
Courau, Tristan;Nehar-Belaid, Djamel;Klatzmann, David
通讯作者：
Klatzmann, David
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
8.8
作者：
Alfaro, C.;Suarez, N.;Gonzalez, A.;Solano, S.;Erro, L.;Dubrot, J.;Palazon, A.;Hervas-Stubbs, S.;Gurpide, A.;Lopez-Picazo, J. M.;Grande-Pulido, E.;Melero, I.;Perez-Gracia, J. L.
通讯作者：
Perez-Gracia, J. L.