Chemokine-driven lymphocyte infiltration: an early intratumoural event determining long-term survival in resectable hepatocellular carcinoma.
Chemokine-driven lymphocyte infiltration: an early intratumoural event determining long-term survival in resectable hepatocellular carcinoma.
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DOI：
10.1136/gutjnl-2011-300509
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发表时间：
2012-03
期刊：
影响因子：
24.5
通讯作者：
Abastado JP
中科院分区：
文献类型：
--
作者：
Chew V;Chen J;Lee D;Loh E;Lee J;Lim KH;Weber A;Slankamenac K;Poon RT;Yang H;Ooi LL;Toh HC;Heikenwalder M;Ng IO;Nardin A;Abastado JP
肝细胞癌（HCC）是一种异质性疾病，预后差，预测患者生存的方法有限。已知浸润肿瘤的免疫细胞的性质会影响临床结果。然而，调节这种渗透的分子事件需要进一步了解。在这里，研究了肿瘤微环境中表达的免疫基因预测疾病进展的能力。使用定量PCR分析了57名新加坡患者切除的肿瘤组织中14种免疫基因的表达。最近模板预测方法用于推导和测试来自该训练队列的预后特征。然后在来自香港和苏黎世的98名患者的独立队列中验证签名。通过原位标记鉴定表达这些关键免疫基因的肿瘤内成分。使用HCC细胞系SNU-182在体外分析这些基因的调控。鉴定的14个免疫基因签名预测训练队列（p=0.0004和HR=5.2）和验证队列（p=0.0051和HR=2.5）中的患者存活，而不考虑患者种族和疾病病因。重要的是，它可以预测早期疾病（I期和II期）患者的生存率，而经典的临床参数提供的信息有限。晚期疾病III期和IV期缺乏预测能力强调必须早期建立保护性免疫微环境，以显著影响疾病进展。该特征包括趋化因子基因CXCL 10、CCL 5和CCL 2，其表达与辅助性T细胞1（Th 1）、CD 8 + T和自然杀伤（NK）细胞的标志物相关。炎性细胞因子（肿瘤坏死因子α、干扰素γ）和Toll样受体3配体刺激这些趋化因子的肿瘤内产生，这些趋化因子驱动T和NK细胞的肿瘤浸润，导致癌细胞死亡增强。一个14个免疫基因签名，它识别了淋巴细胞驱动肿瘤浸润的分子线索，准确地预测了HCC患者的生存率，特别是在早期疾病中。
Hepatocellular carcinoma (HCC) is a heterogeneous disease with poor prognosis and limited methods for predicting patient survival. The nature of the immune cells that infiltrate tumours is known to impact clinical outcome. However, the molecular events that regulate this infiltration require further understanding. Here the ability of immune genes expressed in the tumour microenvironment to predict disease progression was investigated. Using quantitative PCR, the expression of 14 immune genes in resected tumour tissues from 57 Singaporean patients was analysed. The nearest-template prediction method was used to derive and test a prognostic signature from this training cohort. The signature was then validated in an independent cohort of 98 patients from Hong Kong and Zurich. Intratumoural components expressing these critical immune genes were identified by in situ labelling. Regulation of these genes was analysed in vitro using the HCC cell line SNU-182. The identified 14 immune-gene signature predicts patient survival in both the training cohort (p=0.0004 and HR=5.2) and the validation cohort (p=0.0051 and HR=2.5) irrespective of patient ethnicity and disease aetiology. Importantly, it predicts the survival of patients with early disease (stages I and II), for whom classical clinical parameters provide limited information. The lack of predictive power in late disease stages III and IV emphasises that a protective immune microenvironment has to be established early in order to impact disease progression significantly. This signature includes the chemokine genes CXCL10, CCL5 and CCL2, whose expression correlates with markers of T helper 1 (Th1), CD8+ T and natural killer (NK) cells. Inflammatory cytokines (tumour necrosis factor α, interferon γ) and Toll-like receptor 3 ligands stimulate intratumoural production of these chemokines which drive tumour infiltration by T and NK cells, leading to enhanced cancer cell death. A 14 immune-gene signature, which identifies molecular cues driving tumour infiltration by lymphocytes, accurately predicts survival of patients with HCC especially in early disease.
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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：
11.5
作者：
Bergmann, Christoph;Strauss, Laura;Whiteside, Theresa L.
通讯作者：
Whiteside, Theresa L.
影响因子：
13.5
作者：
Matsuzaki, Koichi;Murata, Miki;Seki, Toshihito
通讯作者：
Seki, Toshihito
影响因子：
64.5
作者：
Kuilman, Thomas;Michaloglou, Chrysiis;Peeper, Daniel S.
通讯作者：
Peeper, Daniel S.
DOI：
10.1056/nejmoa0804525
发表时间：
2008-11-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hoshida Y;Villanueva A;Kobayashi M;Peix J;Chiang DY;Camargo A;Gupta S;Moore J;Wrobel MJ;Lerner J;Reich M;Chan JA;Glickman JN;Ikeda K;Hashimoto M;Watanabe G;Daidone MG;Roayaie S;Schwartz M;Thung S;Salvesen HB;Gabriel S;Mazzaferro V;Bruix J;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR