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

Authors

Bogang Wu, Department of Biochemistry & Molecular Medicine, The George Washington University, Washington, DC, 20037, USA.
Xiaowen Zhang, Department of Biochemistry & Molecular Medicine, The George Washington University, Washington, DC, 20037, USA.
Huai-Chin Chiang, Department of Biochemistry & Molecular Medicine, The George Washington University, Washington, DC, 20037, USA.
Haihui Pan, Department of Biochemistry & Molecular Medicine, The George Washington University, Washington, DC, 20037, USA.
Bin Yuan, Department of Biochemistry & Molecular Medicine, The George Washington University, Washington, DC, 20037, USA.
Payal Mitra, Department of Anatomy & Cell Biology, The George Washington University, Washington, DC, 20037, USA.
Leilei Qi, Department of Anatomy & Cell Biology, The George Washington University, Washington, DC, 20037, USA.
Hayk Simonyan, Department of Pharmacology & Physiology, The George Washington University, Washington, DC, 20037, USA.
Colin N. Young, Department of Pharmacology & Physiology, The George Washington University, Washington, DC, 20037, USA.
Eric Yvon, Department of Medicine, The George Washington University Cancer Center School of Medicine & Health Sciences, The George Washington University, Washington, DC, 20037, USA.
Yanfen Hu, Department of Anatomy & Cell Biology, The George Washington University, Washington, DC, 20037, USA.
Nu Zhang, Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX, 78229, USA.
Rong Li, Department of Biochemistry & Molecular Medicine, The George Washington University, Washington, DC, 20037, USA. rli69@gwu.edu.

Document Type

Journal Article

Publication Date

4-20-2022

Journal

Nature communications

Volume

13

Issue

1

DOI

10.1038/s41467-022-29869-2

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.

APA Citation

Wu, Bogang; Zhang, Xiaowen; Chiang, Huai-Chin; Pan, Haihui; Yuan, Bin; Mitra, Payal; Qi, Leilei; Simonyan, Hayk; Young, Colin N.; Yvon, Eric; Hu, Yanfen; Zhang, Nu; and Li, Rong, "RNA polymerase II pausing factor NELF in CD8 T cells promotes antitumor immunity" (2022). GW Authored Works. Paper 771.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/771

Department

Biochemistry and Molecular Medicine