Liver Cancer Immunity.
Liver Cancer Immunity.
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DOI：
10.1002/hep.31416
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
El-Khoueiry AB
中科院分区：
文献类型：
--
作者：
Ilyas SI;Wang J;El-Khoueiry AB
肝细胞癌是最常见的肝癌，占原发性肝癌的80%-90%以上。肝细胞癌也是癌症特有的死亡的主要原因，估计是全世界与癌症相关的死亡的第四大常见原因。(1)胆管细胞癌(CCA)是仅次于肝细胞癌的第二大原发性肝脏恶性肿瘤。尽管CCA的总发病率在近几十年来有所增加，但5年总存活率(OS)仍然不到10%。(2)潜在的根治性手术切除或肝移植是早期疾病患者的一小部分选择。然而，大多数原发性肝癌患者都患有晚期疾病，不适合手术治疗。系统治疗晚期肝癌的疗效有限。因此，有必要开发有效的医疗疗法。在过去的十年里，免疫肿瘤学改变了癌症的治疗。免疫检查点在维持生理条件下的自身耐受中是必不可少的。(3)肿瘤通过激活免疫检查点，如程序性死亡-1(PD-1)及其配体PD-L1，以及细胞毒性T淋巴细胞相关蛋白4(CTLA-4)，来参与抗肿瘤免疫反应。免疫检查点抑制(ICI)使用针对PD-1/PD-L1和CTLA-4的单抗，释放先前存在的免疫，特别是效应CD8+T细胞。(3)ICI疗法对部分患者具有持久的疗效。然而，大多数患者对ICI单一疗法没有反应。肿瘤免疫微环境(时间)影响对免疫治疗的反应。时间大致分为T细胞浸润性-排除性、浸润性-炎症性或浸润性三级淋巴结构。(4)因此，加强对时间免疫生物学的了解将是开发下一代免疫疗法的关键。
Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for over 80%-90% of primary liver cancers. HCC is also a leading cause of cancer-specific death, estimated to be the fourth most common cause of cancerrelated mortality worldwide.(1) Cholangiocarcinoma (CCA) is the second-most common primary hepatic malignancy after HCC. Although the overall incidence of CCA has increased over recent decades, the 5-year overall survival (OS) remains less than 10%.(2) Potentially curative surgical resection or liver transplantation are options for the small subset of patients with early-stage disease. However, most patients with primary liver cancer present with advanced stage disease not amenable to surgical options. Systemic therapies for advanced stage liver cancer have limited efficacy. Hence, there is an essential need for the development of effective medical therapies. Immuno-oncology has transformed cancer treatment over the past decade. Immune checkpoints are essential in the maintenance of self-tolerance under physiologic conditions.(3) Tumors co-opt the antitumor immune response by activating immune checkpoints such as programmed death-1 (PD-1) and its ligand PD-L1, as well as cytotoxic T-lymphocyteassociated protein 4 (CTLA-4). Immune checkpoint inhibition (ICI), using monoclonal antibodies targeting PD-1/PD-L1 and CTLA-4, unleashes preexisting immunity, especially effector CD8+ T cells.(3) ICI therapies have had substantial benefit with durable responses for a subset of patients. However, most patients do not respond to ICI monotherapy. The tumor immune microenvironment (TIME) affects response to immunotherapies. TIMEs are broadly classified into T cell infiltrated-excluded, infiltrated-inflamed, or infiltrated with tertiary lymphoid structures.(4) Hence, an enhanced understanding of the immunobiology of TIME will be essential in the development of next-generation immunotherapies.(4)
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影响因子：
10.1
作者：
Gabrilovich DI
通讯作者：
Gabrilovich DI
肝外胆管癌患者的肿瘤炎性和免疫细胞。
影响因子：
8.8
作者：
Kitano Y;Okabe H;Yamashita YI;Nakagawa S;Saito Y;Umezaki N;Tsukamoto M;Yamao T;Yamamura K;Arima K;Kaida T;Miyata T;Mima K;Imai K;Hashimoto D;Komohara Y;Chikamoto A;Ishiko T;Baba H
通讯作者：
Baba H
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
13.5
作者：
Flecken, Tobias;Schmidt, Nathalie;Hild, Sandra;Gostick, Emma;Drognitz, Oliver;Zeiser, Robert;Schemmer, Peter;Bruns, Helge;Eiermann, Thomas;Price, David A.;Blum, Hubert E.;Neumann-Haefelin, Christoph;Thimme, Robert
通讯作者：
Thimme, Robert
影响因子：
50.3
作者：
Dapito DH;Mencin A;Gwak GY;Pradere JP;Jang MK;Mederacke I;Caviglia JM;Khiabanian H;Adeyemi A;Bataller R;Lefkowitch JH;Bower M;Friedman R;Sartor RB;Rabadan R;Schwabe RF
通讯作者：
Schwabe RF