LIMIT is an immunogenic lncRNA in cancer immunity and immunotherapy

Gaopeng Li, Ilona Kryczek, Jutaek Nam, Xiong Li, Shasha Li, Jing Li, Shuang Wei, Sara Grove, Linda Vatan, Jiajia Zhou, Wan Du, Heng Lin, Ton Wang, Chitra Subramanian, James J. Moon, Marcin Cieslik, Mark Cohen, Weiping Zou

Research output: Contribution to journalArticlepeer-review


Major histocompatibility complex-I (MHC-I) presents tumour antigens to CD8+ T cells and triggers anti-tumour immunity. Humans may have 30,000–60,000 long noncoding RNAs (lncRNAs). However, it remains poorly understood whether lncRNAs affect tumour immunity. Here, we identify a lncRNA, lncRNA inducing MHC-I and immunogenicity of tumour (LIMIT), in humans and mice. We found that IFNγ stimulated LIMIT, LIMIT cis-activated the guanylate-binding protein (GBP) gene cluster and GBPs disrupted the association between HSP90 and heat shock factor-1 (HSF1), thereby resulting in HSF1 activation and transcription of MHC-I machinery, but not PD-L1. RNA-guided CRISPR activation of LIMIT boosted GBPs and MHC-I, and potentiated tumour immunogenicity and checkpoint therapy. Silencing LIMIT, GBPs and/or HSF1 diminished MHC-I, impaired antitumour immunity and blunted immunotherapy efficacy. Clinically, LIMIT, GBP- and HSF1-signalling transcripts and proteins correlated with MHC-I, tumour-infiltrating T cells and checkpoint blockade response in patients with cancer. Together, we demonstrate that LIMIT is a cancer immunogenic lncRNA and the LIMIT–GBP–HSF1 axis may be targetable for cancer immunotherapy.

Original languageEnglish (US)
Pages (from-to)526-537
Number of pages12
JournalNature Cell Biology
Issue number5
StatePublished - May 2021
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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