Tumor-Intrinsic Mechanisms Regulating Immune Exclusion in Liver Cancers.
Tumor-Intrinsic Mechanisms Regulating Immune Exclusion in Liver Cancers.
复制标题
调节肝癌免疫排斥的肿瘤内在机制。
DOI：
10.3389/fimmu.2021.642958
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发表时间：
2021
影响因子：
7.3
通讯作者：
Lujambio A
中科院分区：
文献类型：
--
作者：
Lindblad KE;Ruiz de Galarreta M;Lujambio A
肝癌是世界范围内癌症相关死亡的第四大原因，是一个主要的全球健康问题。肝细胞癌（HCC）是最常见的肝癌类型，与令人沮丧的生存结局相关，传统上几乎没有可用的治疗选择。事实上，直到2017年，晚期HCC的治疗选择仅限于广泛作用的酪氨酸激酶抑制剂，包括索拉非尼，索拉非尼已成为十多年的标准治疗。自2017年以来，包括pembrolizumab，nivolumab，ipilumumab，atezolizumab和贝伐单抗在内的多种单一和联合免疫疗法已被FDA批准用于治疗晚期HCC，其患者的反应率范围为20%至30%。然而，这也意味着约70%的患者对这种治疗没有反应，并且目前对这些免疫疗法的作用机制以及促进患者分层的反应预测因素知之甚少。随着最近免疫疗法在HCC中的成功，迫切需要了解肿瘤免疫逃避和对这些免疫疗法的抗性的机制，以鉴定抗性或应答的生物标志物。这将使更好的患者分层以及合理设计联合免疫疗法，以恢复耐药患者的敏感性。本文旨在总结目前对肝癌免疫逃逸的内在机制的认识，特别是在HCC的背景下。
Representing the fourth leading cause of cancer-related mortality worldwide, liver cancers constitute a major global health concern. Hepatocellular carcinoma (HCC), the most frequent type of liver cancer, is associated with dismal survival outcomes and has traditionally had few treatment options available. In fact, up until 2017, treatment options for advanced HCC were restricted to broad acting tyrosine kinase inhibitors, including Sorafenib, which has been the standard of care for over a decade. Since 2017, a multitude of mono- and combination immunotherapies that include pembrolizumab, nivolumab, ipilumumab, atezolizumab, and bevacizumab have been FDA-approved for the treatment of advanced HCC with unprecedented response rates ranging from 20 to 30% of patients. However, this also means that ~70% of patients do not respond to this treatment and currently very little is known regarding mechanisms of action of these immunotherapies as well as predictors of response to facilitate patient stratification. With the recent success of immunotherapies in HCC, there is a pressing need to understand mechanisms of tumor immune evasion and resistance to these immunotherapies in order to identify biomarkers of resistance or response. This will enable better patient stratification as well as the rational design of combination immunotherapies to restore sensitivity in resistant patients. The aim of this review is to summarize the current knowledge to date of tumor-intrinsic mechanisms of immune escape in liver cancer, specifically in the context of HCC.
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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
影响因子：
11.2
作者：
Hoshida Y;Nijman SM;Kobayashi M;Chan JA;Brunet JP;Chiang DY;Villanueva A;Newell P;Ikeda K;Hashimoto M;Watanabe G;Gabriel S;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
4.7
作者：
Li, Wenli;Wang, Huimei;Liu, Jun
通讯作者：
Liu, Jun
影响因子：
158.5
作者：
Finn, Richard S.;Qin, Shukui;Cheng, Ann-Lii
通讯作者：
Cheng, Ann-Lii