PT  - JOURNAL ARTICLE
AU  - Guo, Weiwei
AU  - Wang, Yue
AU  - Yang, Min
AU  - Wang, Zehua
AU  - Wang, Yifei
AU  - Chaurasia, Smriti
AU  - Wu, Zhiyuan
AU  - Zhang, Min
AU  - Yadav, Ghanshyam Singh
AU  - Rathod, Sanjay
AU  - Concha-Benavente, Fernando
AU  - Fernandez, Christian
AU  - Li, Song
AU  - Xie, Wen
AU  - Ferris, Robert L.
AU  - Kammula, Udai S.
AU  - Lu, Binfeng
AU  - Yang, Da
TI  - LincRNA-immunity landscape analysis identifies EPIC1 as a regulator of tumor immune evasion and immunotherapy resistance
AID  - 10.1126/sciadv.abb3555
DP  - 2021 Feb 01
TA  - Science Advances
PG  - eabb3555
VI  - 7
IP  - 7
4099  - http://advances.sciencemag.org/content/7/7/eabb3555.short
4100  - http://advances.sciencemag.org/content/7/7/eabb3555.full
SO  - Sci Adv2021 Feb 01; 7
AB  - Through an integrative analysis of the lincRNA expression and tumor immune response in 9,626 tumor samples across 32 cancer types, we developed a lincRNA-based immune response (LIMER) score that can predict the immune cells infiltration and patient prognosis in multiple cancer types. Our analysis also identified tumor-specific lincRNAs, including EPIC1, that potentially regulate tumor immune response in multiple cancer types. Immunocompetent mouse models and in vitro co-culture assays demonstrated that EPIC1 induces tumor immune evasion and resistance to immunotherapy by suppressing tumor cell antigen presentation. Mechanistically, lincRNA EPIC1 interacts with the histone methyltransferase EZH2, leading to the epigenetic silencing of IFNGR1, TAP1/2, ERAP1/2, and MHC-I genes. Genetic and pharmacological inhibition of EZH2 abolish EPIC1’s immune-related oncogenic effect and its suppression of interferon-γ signaling. The EPIC1-EZH2 axis emerges as a potential mechanism for tumor immune evasion that can serve as therapeutic targets for immunotherapy.