Context-specific functions of chromatin remodellers in development and disease DOI
Sai Gourisankar, A. Krokhotin,

Wendy Wenderski

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(5), P. 340 - 361

Published: Nov. 24, 2023

Language: Английский

T cells in health and disease DOI Creative Commons
Lina Sun, Yanhong Su, Anjun Jiao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 19, 2023

T cells are crucial for immune functions to maintain health and prevent disease. cell development occurs in a stepwise process the thymus mainly generates CD4

Language: Английский

Citations

367
Stem-like exhausted and memory CD8+ T cells in cancer DOI
Thomas Gebhardt, Simone L. Park, Ian A. Parish

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(11), P. 780 - 798

Published: Oct. 11, 2023

Language: Английский

Citations

73
Extracellular acidosis restricts one-carbon metabolism and preserves T cell stemness DOI Creative Commons

Hongcheng Cheng,

Yajing Qiu, Yue Xu

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(2), P. 314 - 330

Published: Jan. 30, 2023

The accumulation of acidic metabolic waste products within the tumor microenvironment inhibits effector functions tumor-infiltrating lymphocytes (TILs). However, it remains unclear how an environment affects T cell metabolism and differentiation. Here we show that prolonged exposure to acid reprograms intracellular mitochondrial fitness preserves stemness. Mechanistically, elevated extracellular acidosis impairs methionine uptake via downregulation SLC7A5, therefore altering H3K27me3 deposition at promoters key stemness genes. These changes promote maintenance a 'stem-like memory' state improve long-term in vivo persistence anti-tumor efficacy mice. Our findings not only reveal unexpected capacity maintain stem-like properties cells, but also advance our understanding

Language: Английский

Citations

70
Hallmarks of CD8+ T cell dysfunction are established within hours of tumor antigen encounter before cell division DOI
Michael Rudloff, Paul Zumbo, Natalie R. Favret

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(9), P. 1527 - 1539

Published: Aug. 3, 2023

Language: Английский

Citations

70
Advancing CAR T cell therapy through the use of multidimensional omics data DOI
Jingwen Yang, Yamei Chen, Ying Jing

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(4), P. 211 - 228

Published: Jan. 31, 2023

Language: Английский

Citations

66
Principles and therapeutic applications of adaptive immunity DOI Creative Commons
Hongbo Chi, Marion Pepper, Paul G. Thomas

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(9), P. 2052 - 2078

Published: April 1, 2024

Adaptive immunity provides protection against infectious and malignant diseases. These effects are mediated by lymphocytes that sense respond with targeted precision to perturbations induced pathogens tissue damage. Here, we review key principles underlying adaptive orchestrated distinct T cell B populations their extensions disease therapies. We discuss the intracellular intercellular processes shaping antigen specificity recognition in immune activation lymphocyte functions mediating effector memory responses. also describe how balance protective autoimmunity immunopathology, including during tolerance, response chronic stimulation, adaptation non-lymphoid tissues coordinating homeostasis. Finally, extracellular signals cell-intrinsic programs underpinning conclude summarizing advances vaccination engineering responses for therapeutic interventions. A deeper understanding of these holds promise uncovering new means improve human health.

Language: Английский

Citations

65
Beggars banquet: Metabolism in the tumor immune microenvironment and cancer therapy DOI Creative Commons
Weiping Zou, Douglas R. Green

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(7), P. 1101 - 1113

Published: June 29, 2023

Language: Английский

Citations

50
Stepwise activities of mSWI/SNF family chromatin remodeling complexes direct T cell activation and exhaustion DOI Creative Commons
Elena Battistello,

Kimberlee A. Hixon,

Dawn E. Comstock

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(8), P. 1216 - 1236.e12

Published: March 20, 2023

Highly coordinated changes in gene expression underlie T cell activation and exhaustion. However, the mechanisms by which such programs are regulated how these may be targeted for therapeutic benefit remain poorly understood. Here, we comprehensively profile genomic occupancy of mSWI/SNF chromatin remodeling complexes throughout acute chronic stimulation, finding that stepwise localization over transcription factor binding sites direct site-specific accessibility leading to distinct phenotypes. Notably, perturbation using genetic clinically relevant chemical strategies enhances persistence cells with attenuated exhaustion hallmarks increased memory features vitro vivo. Finally, pharmacologic inhibition improves CAR-T expansion results improved anti-tumor control These findings reveal central role coordination nominate small-molecule-based improvement current immunotherapy protocols.

Language: Английский

Citations

44
ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity DOI

Matthew B. Maxwell,

Marianne S. Hom, Jawoon Yi

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(13), P. 3390 - 3408.e19

Published: May 15, 2024

Language: Английский

Citations

34
Epigenome editing technologies for discovery and medicine DOI

Sean R. McCutcheon,

Dahlia Rohm,

Nahid Iglesias

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: 42(8), P. 1199 - 1217

Published: July 29, 2024

Language: Английский

Citations

18