Tumour inflammasome‐derived IL‐1β recruits neutrophils and improves local recurrence‐free survival in EBV‐induced nasopharyngeal carcinoma

• Published in: EMBO molecular medicine Vol. 4; no. 12; pp. 1276 - 1293
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.12.2012; EMBO Press; WILEY-VCH Verlag
• Subjects: Animals; cancer; Cancer therapies; Carcinogenesis; Carcinoma; Chemotherapy; Cohort Studies; Deoxyribonucleic acid; DNA; Epstein-Barr virus; Gene expression; Herpesvirus 4, Human - pathogenicity; Humans; Immunostimulation; Infections; inflammasome; Inflammasomes; Inflammasomes - immunology; Inflammasomes - metabolism; Inflammation; Inflammation - metabolism; Interleukin-1beta - metabolism; Leukocytes (neutrophilic); Medical prognosis; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mitochondrial DNA; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - immunology; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - virology; neutrophil; Neutrophil Infiltration; Neutrophils; Neutrophils - metabolism; prognosis; Radiation; Reactive oxygen species; Reactive Oxygen Species - metabolism; Retrospective Studies; Studies; Therapeutic applications; therapy; Throat cancer; Tumors; Taiwan
• ISSN: 1757-4676; 1757-4684
• DOI: 10.1002/emmm.201201569

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. Inflammasomes detect infection and trigger inflammation. The authors find that in Epstein‐Barr virusassociated nasopharyngeal carcinoma, inflammasomes recruit neutrophils, which produce IL‐1beta and thereby inhibit tumor growth.