Advances in immunotherapy for hepatocellular carcinoma.
Advances in immunotherapy for hepatocellular carcinoma.
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肝细胞癌免疫疗法的进展。
DOI：
10.1038/s41575-021-00438-0
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Melero I
中科院分区：
文献类型：
--
作者：
Sangro B;Sarobe P;Hervás-Stubbs S;Melero I
肝细胞癌（HCC）是一种流行性疾病，其进展受免疫系统调节。全身治疗用于晚期，直到2017年仅包括抗血管生成酪氨酸激酶抑制剂（TKI）。检查点抑制剂的免疫治疗在一部分患者中显示出较强的抗肿瘤活性，抗PDL1抗体atezolizumab和VEGF中和抗体贝伐珠单抗的组合已经或即将成为HCC一线治疗的标准治疗，而抗PD1药物nivolumab和pembrolizumab在几个地区用于TKI后。其他免疫策略，如过继性T细胞转移，疫苗接种或病毒治疗尚未表现出一致的临床活性。HCC检查点免疫治疗中尚未解决的主要挑战是发现和验证预测性生物标志物，将治疗推进到疾病的早期阶段，将治疗应用于肝功能障碍患者以及发现更有效的组合或顺序方法。与其他全身或局部治疗的组合被认为是HCC中最有希望的机会，其中一些已经在大规模临床试验中进行了评估。本综述提供了最新的信息，最好地利用目前可用的免疫疗法在肝癌和正在开发的治疗策略。免疫干预可能是治疗肝癌的有效手段。本综述提供了目前可用的免疫疗法在肝细胞癌中的临床应用，反应和耐药机制以及正在开发的治疗策略的最新信息。多种免疫机制在肝细胞癌（HCC）的发生发展中起重要作用，并与预后相关。靶向PD1、PDL1和CTLA4的检查点抑制剂对晚期HCC具有活性、耐受性和临床获益。目前，晚期HCC的最佳一线治疗方案是联合应用atezolizumab阻断PDL 1和贝伐单抗阻断VEGF。迄今为止，几乎完全缺乏合适的生物标志物来指导检查点抑制剂及其组合在HCC中的开发。免疫治疗可能在HCC的早期阶段与局部和局部区域干预协同作用。其他有希望的HCC免疫治疗形式，如额外的检查点抑制剂，过继细胞转移，疫苗接种和病毒治疗正在积极寻求。
Hepatocellular carcinoma (HCC) is a prevalent disease with a progression that is modulated by the immune system. Systemic therapy is used in the advanced stage and until 2017 consisted only of antiangiogenic tyrosine kinase inhibitors (TKIs). Immunotherapy with checkpoint inhibitors has shown strong anti-tumour activity in a subset of patients and the combination of the anti-PDL1 antibody atezolizumab and the VEGF-neutralizing antibody bevacizumab has or will soon become the standard of care as a first-line therapy for HCC, whereas the anti-PD1 agents nivolumab and pembrolizumab are used after TKIs in several regions. Other immune strategies such as adoptive T-cell transfer, vaccination or virotherapy have not yet demonstrated consistent clinical activity. Major unmet challenges in HCC checkpoint immunotherapy are the discovery and validation of predictive biomarkers, advancing treatment to earlier stages of the disease, applying the treatment to patients with liver dysfunction and the discovery of more effective combinatorial or sequential approaches. Combinations with other systemic or local treatments are perceived as the most promising opportunities in HCC and some are already under evaluation in large-scale clinical trials. This Review provides up-to-date information on the best use of currently available immunotherapies in HCC and the therapeutic strategies under development. Immunotherapeutic interventions might be effective tools for the treatment of hepatocellular carcinoma. This Review provides up-to-date information on the clinical use of currently available immunotherapies in hepatocellular carcinoma, the mechanisms of response and resistance, and the therapeutic strategies under development. Multiple immune mechanisms are important in the development and progression of hepatocellular carcinoma (HCC) and correlate with prognosis. Checkpoint inhibitors targeting PD1 and PDL1 and CTLA4 are active, tolerable and clinically beneficial against advanced HCC. At present, the best available first-line treatment for advanced HCC is a combination of PDL1 blockade with atezolizumab and VEGF blockade with bevacizumab. There is as yet an almost complete lack of suitable biomarkers to guide the development of checkpoint inhibitors and their combinations in HCC. Immunotherapy is likely to synergize with local and locoregional interventions in earlier stages of HCC. Other promising forms of immunotherapy for HCC such as additional checkpoint inhibitors, adoptive cell transfer, vaccination and virotherapy are being actively pursued.
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影响因子：
11.5
作者：
Butterfield, LH;Ribas, A;Economou, JS
通讯作者：
Economou, JS
影响因子：
13.5
作者：
Calderaro, Julien;Rousseau, Benoit;Pawlotsky, Jean-Michel
通讯作者：
Pawlotsky, Jean-Michel
影响因子：
13
作者：
Cappuzzello, Elisa;Sommaggio, Roberta;Rosato, Antonio
通讯作者：
Rosato, Antonio
DOI：
10.1007/s00262-018-2190-4
发表时间：
2018-08
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Brown ZJ;Yu SJ;Heinrich B;Ma C;Fu Q;Sandhu M;Agdashian D;Zhang Q;Korangy F;Greten TF
通讯作者：
Greten TF
影响因子：
7.2
作者：
Cariani, Elisabetta;Pilli, Massimo;Missale, Gabriele
通讯作者：
Missale, Gabriele