Translational Considerations to Improve Response and Overcome Therapy Resistance in Immunotherapy for Hepatocellular Carcinoma.
Translational Considerations to Improve Response and Overcome Therapy Resistance in Immunotherapy for Hepatocellular Carcinoma.
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DOI：
10.3390/cancers12092495
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发表时间：
2020-09-03
期刊：
影响因子：
5.2
通讯作者：
Marquardt JU
中科院分区：
文献类型：
--
作者：
Heinrich S;Castven D;Galle PR;Marquardt JU
免疫治疗方法成为一种有前途的治疗选择，也是肝癌研究的一个密集领域。尽管在临床前研究中取得了令人鼓舞的结果，但在III期临床试验中仅报告了中等缓解率，并且仍然缺少预测性生物标志物。因此，翻译考虑对于克服对免疫疗法的抗性是重要的。本文综述了肝细胞癌（HCC）免疫治疗反应的潜在预测因素以及治疗耐药的潜在机制。此外，我们将讨论转化的考虑，以克服肝癌的治疗耐药性，提高整体反应率。在过去的十年中，全身治疗的进展显着改善了原发性肝癌的结局。最近，精确的肿瘤学和免疫学方法成为密集的科学和临床研究的焦点。在此，临床前研究显示了有希望的结果，具有高响应率和总生存期的改善。然而，III期临床试验的结果显示，只有一小部分肝细胞癌（HCC）患者对治疗有反应，并且仅显示中等客观缓解率。此外，预测性分子特征在很大程度上缺失。因此，合适的试验设计已成为新化合物成功的关键因素。此外，来自转化研究的越来越多的知识表明靶向肿瘤免疫环境以克服对免疫疗法的抗性的重要性。因此，不同的免疫疗法与其他治疗方式（包括抗体、酪氨酸激酶抑制剂或局部疗法）的组合非常有希望。然而，肝癌免疫治疗失败的机制尚未完全了解，免疫系统和细胞肿瘤组成的调节在这种情况下特别相关。总之，越来越清楚的是，需要定制免疫治疗和个性化方法来改善肝癌的疗效和患者结局。本文综述了目前的知识以及翻译的考虑，以克服原发性肝癌免疫治疗的治疗耐药性的概述。
Immunotherapeutic approaches became a promising treatment option and an intensive field of research in liver cancer. Despite promising results in preclinical studies, only moderate response rates have been reported in phase III clinical trials and predictive biomarkers are still missing. Therefore, translational considerations are important to overcome resistance to immunotherapy. This article reviews potential predictors for response to immunotherapy in hepatocellular carcinoma (HCC) as well as potential mechanisms for therapy resistance. Further, we will discuss translational considerations to overcome therapy resistance in HCC and improve overall response rates. Over the last decade, progress in systemic therapies significantly improved the outcome of primary liver cancer. More recently, precision oncological and immunotherapeutic approaches became the focus of intense scientific and clinical research. Herein, preclinical studies showed promising results with high response rates and improvement of overall survival. However, results of phase III clinical trials revealed that only a subfraction of hepatocellular carcinoma (HCC) patients respond to therapy and display only moderate objective response rates. Further, predictive molecular characteristics are largely missing. In consequence, suitable trial design has emerged as a crucial factor for the success of a novel compound. In addition, increasing knowledge from translational studies indicate the importance of targeting the tumor immune environment to overcome resistance to immunotherapy. Thus, combination of different immunotherapies with other treatment modalities including antibodies, tyrosine kinase inhibitors, or local therapies is highly promising. However, the mechanisms of failure to respond to immunotherapy in liver cancer are still not fully understood and the modulation of the immune system and cellular tumor composition is particularly relevant in this context. Altogether, it is increasingly clear that tailoring of immunotherapy and individualized approaches are required to improve efficacy and patient outcome in liver cancer. This review provides an overview of the current knowledge as well as translational considerations to overcome therapy resistance in immunotherapy of primary liver cancer.
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影响因子：
1.2
作者：
Adcock, Charles S.;Puneky, Louis V.;Campbell, Garth S.
通讯作者：
Campbell, Garth S.
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
DOI：
10.1158/1078-0432.ccr-19-2923
发表时间：
2020-10-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bresnahan E;Lindblad KE;Ruiz de Galarreta M;Lujambio A
通讯作者：
Lujambio A
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：
168.9
作者：
Bruix, Jordi;Qin, Shukui;Han, Guohong
通讯作者：
Han, Guohong