Tumour inflammasome-derived IL-1β recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma.
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.
Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
Lih-Chyang
LC
Chen
Li-Jie
LJ
Wang
Nang-Ming
NM
Tsang
David M
DM
Ojcius
Chia-Chun
CC
Chen
Chun-Nan
CN
Ouyang
Chuen
C
Hsueh
Ying
Y
Liang
Kai-Ping
KP
Chang
Chiu-Chin
CC
Chen
Yu-Sun
YS
Chang
D000818:Animals; D002277:Carcinoma; D015331:Cohort Studies; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012189:Retrospective Studies
D058847:Inflammasomes; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species