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RNA polymerase II pausing factor NELF in CD8+ T cells promotes antitumor immunity

Author

Listed:
  • Bogang Wu

    (The George Washington University)

  • Xiaowen Zhang

    (The George Washington University)

  • Huai-Chin Chiang

    (The George Washington University)

  • Haihui Pan

    (The George Washington University)

  • Bin Yuan

    (The George Washington University)

  • Payal Mitra

    (The George Washington University)

  • Leilei Qi

    (The George Washington University)

  • Hayk Simonyan

    (The George Washington University)

  • Colin N. Young

    (The George Washington University)

  • Eric Yvon

    (The George Washington University Cancer Center School of Medicine & Health Sciences, The George Washington University)

  • Yanfen Hu

    (The George Washington University)

  • Nu Zhang

    (University of Texas Health San Antonio)

  • Rong Li

    (The George Washington University)

Abstract

T cell factor 1 (TCF1) is required for memory and stem-like CD8+ T cell functions. How TCF1 partners with other transcription factors to regulate transcription remains unclear. Here we show that negative elongation factor (NELF), an RNA polymerase II (Pol II) pausing factor, cooperates with TCF1 in T cell responses to cancer. Deletion of mouse Nelfb, which encodes the NELFB subunit, in mature T lymphocytes impairs immune responses to both primary tumor challenge and tumor antigen-mediated vaccination. Nelfb deletion causes more exhausted and reduced memory T cell populations, whereas its ectopic expression boosts antitumor immunity and efficacy of chimeric antigen receptor T-cell immunotherapy. Mechanistically, NELF is associated with TCF1 and recruited preferentially to the enhancers and promoters of TCF1 target genes. Nelfb ablation reduces Pol II pausing and chromatin accessibility at these TCF1-associated loci. Our findings thus suggest an important and rate-limiting function of NELF in anti-tumor immunity.

Suggested Citation

  • Bogang Wu & Xiaowen Zhang & Huai-Chin Chiang & Haihui Pan & Bin Yuan & Payal Mitra & Leilei Qi & Hayk Simonyan & Colin N. Young & Eric Yvon & Yanfen Hu & Nu Zhang & Rong Li, 2022. "RNA polymerase II pausing factor NELF in CD8+ T cells promotes antitumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29869-2
    DOI: 10.1038/s41467-022-29869-2
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    1. Jieqiong Zhang & Zhenhua Hu & Hwa Hwa Chung & Yun Tian & Kah Weng Lau & Zheng Ser & Yan Ting Lim & Radoslaw M. Sobota & Hwei Fen Leong & Benjamin Jieming Chen & Clarisse Jingyi Yeo & Shawn Ying Xuan T, 2023. "Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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