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

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 i...

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Autores principales: 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, Li, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021285/
https://www.ncbi.nlm.nih.gov/pubmed/35444206
http://dx.doi.org/10.1038/s41467-022-29869-2
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author 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
Li, Rong
author_facet 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
Li, Rong
author_sort Wu, Bogang
collection PubMed
description 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.
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spelling pubmed-90212852022-04-28 RNA polymerase II pausing factor NELF in CD8(+) T cells promotes antitumor immunity 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 Li, Rong Nat Commun Article 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. Nature Publishing Group UK 2022-04-20 /pmc/articles/PMC9021285/ /pubmed/35444206 http://dx.doi.org/10.1038/s41467-022-29869-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Li, Rong
RNA polymerase II pausing factor NELF in CD8(+) T cells promotes antitumor immunity
title RNA polymerase II pausing factor NELF in CD8(+) T cells promotes antitumor immunity
title_full RNA polymerase II pausing factor NELF in CD8(+) T cells promotes antitumor immunity
title_fullStr RNA polymerase II pausing factor NELF in CD8(+) T cells promotes antitumor immunity
title_full_unstemmed RNA polymerase II pausing factor NELF in CD8(+) T cells promotes antitumor immunity
title_short RNA polymerase II pausing factor NELF in CD8(+) T cells promotes antitumor immunity
title_sort rna polymerase ii pausing factor nelf in cd8(+) t cells promotes antitumor immunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021285/
https://www.ncbi.nlm.nih.gov/pubmed/35444206
http://dx.doi.org/10.1038/s41467-022-29869-2
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