ArticleImmunity2022
Human epigenetic and transcriptional T cell differentiation atlas for identifying functional T cell-specific enhancers.
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Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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81citing papers in PubMed
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Who cites it
81 citing papers in PubMed.
- Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion.Nature communications · 2024Trial
- Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients.Science (New York, N.Y.) · 2024Trial
- A single-cell transcriptomic atlas of peripheral blood immune cells spanning progressive canine leishmaniosis.iScience · 2026Article
- Aberrant STAT signaling and T cell dysregulation define a targetable pediatric sepsis endotype.The Journal of clinical investigation · 2026Article
- T cell dysregulation and remodeling in pediatric obesity and weight loss.bioRxiv : the preprint server for biology · 2026Article
- T cell adaptation in chronic infections and tumors.Cellular & molecular immunology · 2026Review
- Fine-tuning BACH2 dosage balances stemness and effector function to enhance antitumor T cell therapy.Nature immunology · 2026Article
- Multi-Omics Analysis of Human Blood Cells Reveals Unique Features of Age-Associated Type 2 CD8 Memory T Cells.Aging cell · 2026Article
- Age-independent and targetable transcription factor networks regulating CD8Cell reports · 2026Article
- Deriving genetic codes for molecular phenotypes from first principles.bioRxiv : the preprint server for biology · 2026Article
- Tissue-resident exhausted and memory CD8Nature immunology · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- A single-cell transcriptomic atlas of peripheral blood immune cells spanning progressive canine leishmaniosis.bioRxiv : the preprint server for biology · 2025Article
- Senescent CD8 T Effector Memory Cells are Functionally Impaired, Enriched in Aging and Disease, and a Barrier to Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Multimodal analysis definesbioRxiv : the preprint server for biology · 2025Article
- CD8⁺ T cell heterogeneity in aging: insights from single-cell profiling.Immunity & ageing : I & A · 2025Review
- Imbalance of stem-like and effector T cell states in children with early type 1 diabetes across conventional and regulatory subsets.Nature communications · 2025Article
- Chromatin repression by PRC2 results in reduced gene expression driving key features of CD8 T cell exhaustion.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Scalable transcription factor mapping uncovers the regulatory dynamics of natural and synthetic transcription factors in human T cell states.bioRxiv : the preprint server for biology · 2025Article
- Faithful modeling of terminal CD8+T cell dysfunction and epigenetic stabilization in vitro.JCI insight · 2025Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors.
Josephine R GilesDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sasikanth ManneDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Elizabeth FreilichDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA.
Derek A OldridgeInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Amy E BaxterDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sangeeth GeorgeDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.
Zeyu ChenDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hua HuangDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA.
Lakshmi ChilukuriDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.
Mary CarberryDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lydia GilesDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nan-Ping P WengLaboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Regina M YoungCenter for Cellular Immunotherapies, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Carl H JuneParker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lynn M SchuchterDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ravi K AmaravadiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Xiaowei XuDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Giorgos C KarakousisAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Tara C MitchellDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alexander C HuangInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Junwei ShiDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA.
E John WherryDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: wherry@pennmedicine.upenn.edu.
Funding
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3MVirus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6MVirology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG, GEORG Michael LAUER · 2009 to 2026
$48.1MSynergies among inhibitory receptors in tolerance, cancer & antiviral immunityP01AI108545 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Dario AA Vignali · 2015 to 2026
$30.8MIMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MModeling HIV CAR-T cell trafficking and persistence in Non-Human PrimatesU19AI149680 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI RILEY, JAMES L. · 2020 to 2024
$13.2MSequencing and Viral Evolution CoreU19AI117950 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2015 to 2019
$12.0MRadiation and checkpoint blockade for cancer immune therapyP01CA210944 · NCI · UNIVERSITY OF PENNSYLVANIA · PI VONDERHEIDE, ROBERT H · 2017 to 2022
$11.5MTargeting exosomal PDL1 to improve immunotherapyP50CA261608 · NCI · WISTAR INSTITUTE · PI VILLANUEVA, JESSIE · 2021 to 2025
$11.3MTargeted Combination Therapy for MelanomaP50CA174523 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2014 to 2018
$11.1MMechanisms Of Transcriptional Regulation in Memory lymphocyte Response and AgingZIAAG000757 · NIA · NATIONAL INSTITUTE ON AGING · PI WENG, NAN-PING PETER · 2009 to 2025
$7.9MTesting the role of BATF as a pioneer transcription factor in effector T cellsR01AI115712 · NIAID · DANA-FARBER CANCER INST · PI KADOCH, CIGALL, WHERRY, E. JOHN · 2015 to 2019
$2.9MNCI NIH HHS F99 CA234842NCI NIH HHS K00 CA234842NCI NIH HHS K08 CA230157NCI NIH HHS P01 CA210944NCI NIH HHS P30 CA016520NCI NIH HHS P50 CA174523NCI NIH HHS P50 CA261608NCI NIH HHS T32 CA009140NHLBI NIH HHS R38 HL143613NIAID NIH HHS P01 AI108545NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI115712NIAID NIH HHS R01 AI155577NIAID NIH HHS U19 AI082630NIAID NIH HHS U19 AI117950NIAID NIH HHS U19 AI149680
Abstract
The clinical benefit of T cell immunotherapies remains limited by incomplete understanding of T cell differentiation and dysfunction. We generated an epigenetic and transcriptional atlas of T cell differentiation from healthy humans that included exhausted CD8 T cells and applied this resource in three ways. First, we identified modules of gene expression and chromatin accessibility, revealing molecular coordination of differentiation after activation and between central memory and effector memory. Second, we applied this healthy molecular framework to three settings-a neoadjuvant anti-PD1 melanoma trial, a basal cell carcinoma scATAC-seq dataset, and autoimmune disease-associated SNPs-yielding insights into disease-specific biology. Third, we predicted genome-wide cis-regulatory elements and validated this approach for key effector genes using CRISPR interference, providing functional annotation and demonstrating the ability to identify targets for non-coding cellular engineering. These studies define epigenetic and transcriptional regulation of human T cells and illustrate the utility of interrogating disease in the context of a healthy T cell atlas.
Indexed as
EpigenomicsLymphocyte ActivationCD8-Positive T-LymphocytesCell DifferentiationChromatinEpigenesis, GeneticHumansChromatinCD8 T cell differentiationCRISPRepigenetic regulationepigenome engineering
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