ORCiD
David M. Ojcius: 0000-0003-1461-4495
Department
Biomedical Sciences
Document Type
Article
Publication Title
EMBO Molecular Medicine
ISSN
1757-4676
Volume
4
Issue
12
DOI
10.1002/emmm.201201569
First Page
1276
Last Page
1293
Publication Date
12-1-2012
Abstract
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.
Recommended Citation
Chen, L.,
Wang, L.,
Tsang, N.,
Ojcius, D. M.,
Chen, C.,
OuYang, C.,
Hsueh, C.,
Liang, Y.,
Chang, K.,
Chen, C.,
&
Chang, Y.
(2012).
Tumour inflammasome-derived IL-1b recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma.
EMBO Molecular Medicine, 4(12), 1276–1293.
DOI: 10.1002/emmm.201201569
https://scholarlycommons.pacific.edu/dugoni-facarticles/22
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