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Tumour inflammasome-derived IL-1b recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma
EMBO Molecular Medicine
  • Lih-Chyang Chen, Chang Gung University
  • Li-Jie Wang, Chang Gung University
  • Nang-Ming Tsang, Chang Gung Memorial Hospital at Lin-Kou
  • David M. Ojcius, University of California, Merced
  • Chia-Chen Chen, Chang Gung University
  • Chun-Nan OuYang, Chang Gung University
  • Chuen Hsueh, Chang Gung University
  • Ying Liang, Chang Gung University
  • Kai-Ping Chang, Chang Gung Memorial Hospital at Lin-Kou
  • Chiu-Chin Chen, Chang Gung University
  • Yu-Sun Chang, Chang Gung University
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Document Type
Article
DOI
10.1002/emmm.201201569
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.
Citation Information
Lih-Chyang Chen, Li-Jie Wang, Nang-Ming Tsang, David M. Ojcius, et al.. "Tumour inflammasome-derived IL-1b recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma" EMBO Molecular Medicine Vol. 4 Iss. 12 (2012) p. 1276 - 1293 ISSN: 1757-4676
Available at: http://works.bepress.com/david-ojcius/232/