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

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

Producción científica: Articlerevisión exhaustiva

7 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Número de artículo2155
PublicaciónNature communications
Volumen13
N.º1
DOI
EstadoPublished - dic 2022

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

Huella

Profundice en los temas de investigación de 'RNA polymerase II pausing factor NELF in CD8+ T cells promotes antitumor immunity'. En conjunto forman una huella única.

Citar esto