Tumour inflammasome-derived IL-1β recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma.
Tumour inflammasome-derived IL-1β recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma.
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DOI：
10.1002/emmm.201201569
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发表时间：
2012-12
影响因子：
11.1
通讯作者：
Chang, Yu-Sun
中科院分区：
文献类型：
--
作者：
Chen, Lih-Chyang;Wang, Li-Jie;Tsang, Nang-Ming;Ojcius, David M.;Chen, Chia-Chun;OuYang, Chun-Nan;Hsueh, Chuen;Liang, Ying;Chang, Kai-Ping;Chen, Chiu-Chin;Chang, Yu-Sun
炎症小体感知感染和细胞损伤，对于通过产生 IL-1β 引发炎症至关重要。在致癌过程中，炎症小体可能通过促进抗肿瘤免疫和诱导致癌因子发挥矛盾的作用。它们在癌症中的功能仍然知之甚少。在这里，我们发现 NLRP3、AIM2 和 RIG-I 炎症小体在 Epstein-Barr 病毒 (EBV) 相关鼻咽癌 (NPC) 中过度表达，并且表达水平与患者生存相关。在肿瘤细胞中，AIM2 和 RIG-I 分别是 EBV 基因组 DNA 和 EBV 编码的小 RNA 诱导 IL-1β 所必需的，而 NLRP3 则对细胞外 ATP 和活性氧做出反应。放疗和化疗可以分别进一步激活 AIM2 和 NLRP3。在小鼠中，肿瘤源性 IL-1β 可通过宿主反应抑制肿瘤生长并提高存活率。从机制上讲，IL-1β介导的抗肿瘤作用依赖于浸润的免疫刺激性中性粒细胞。我们进一步表明，肿瘤相关中性粒细胞的存在与鼻咽癌患者的更好生存显着相关。因此，肿瘤炎性体通过招募中性粒细胞在肿瘤控制中发挥关键作用，其表达水平是患者有利的预后标志物和有希望的治疗靶点。
Inflammasomes sense infection and cellular damage and are critical for triggering inflammation through IL-1β production. In carcinogenesis, inflammasomes may have contradictory roles through facilitating antitumour immunity and inducing oncogenic factors. Their function in cancer remains poorly characterized. Here we show that the NLRP3, AIM2 and RIG-I inflammasomes are overexpressed in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), and expression levels correlate with patient survival. In tumour cells, AIM2 and RIG-I are required for IL-1β induction by EBV genomic DNA and EBV-encoded small RNAs, respectively, while NLRP3 responds to extracellular ATP and reactive oxygen species. Irradiation and chemotherapy can further activate AIM2 and NLRP3, respectively. In mice, tumour-derived IL-1β inhibits tumour growth and enhances survival through host responses. Mechanistically, IL-1β-mediated anti-tumour effects depend on infiltrated immunostimulatory neutrophils. We show further that presence of tumour-associated neutrophils is significantly associated with better survival in NPC patients. Thus, tumour inflammasomes play a key role in tumour control by recruiting neutrophils, and their expression levels are favourable prognostic markers and promising therapeutic targets in patients.
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影响因子：
7.5
作者：
Chen, Lih-Chyang;Chen, Chia-Chun;Hsueh, Chuen
通讯作者：
Hsueh, Chuen
影响因子：
50.3
作者：
Granot Z;Henke E;Comen EA;King TA;Norton L;Benezra R
通讯作者：
Benezra R
影响因子：
7.5
作者：
Caruso, RA;Bellocco, R;Inferrera, C
通讯作者：
Inferrera, C
影响因子：
12.4
作者：
Chen, L-C;Chung, I-C;Chang, Y-S
通讯作者：
Chang, Y-S
DOI：
10.1084/jem.20100050
发表时间：
2010-05-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allen IC;TeKippe EM;Woodford RM;Uronis JM;Holl EK;Rogers AB;Herfarth HH;Jobin C;Ting JP
通讯作者：
Ting JP