Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-07-26

AUTHORS

Mohamed S. Abdel-Hakeem, Sasikanth Manne, Jean-Christophe Beltra, Erietta Stelekati, Zeyu Chen, Kito Nzingha, Mohammed-Alkhatim Ali, John L. Johnson, Josephine R. Giles, Divij Mathew, Allison R. Greenplate, Golnaz Vahedi, E. John Wherry

ABSTRACT

Exhausted CD8 T cells (TEX) are a distinct state of T cell differentiation associated with failure to clear chronic viruses and cancer. Immunotherapies such as PD-1 blockade can reinvigorate TEX cells, but reinvigoration is not durable. A major unanswered question is whether TEX cells differentiate into functional durable memory T cells (TMEM) upon antigen clearance. Here, using a mouse model, we found that upon eliminating chronic antigenic stimulation, TEX cells partially (re)acquire phenotypic and transcriptional features of TMEM cells. These ‘recovering’ TEX cells originated from the T cell factor (TCF-1+) TEX progenitor subset. Nevertheless, the recall capacity of these recovering TEX cells remained compromised as compared to TMEM cells. Chromatin-accessibility profiling revealed a failure to recover core memory epigenetic circuits and maintenance of a largely exhausted open chromatin landscape. Thus, despite some phenotypic and transcriptional recovery upon antigen clearance, exhaustion leaves durable epigenetic scars constraining future immune responses. These results support epigenetic remodeling interventions for TEX cell–targeted immunotherapies. More... »

PAGES

1008-1019

References to SciGraph publications

  • 2018-04-02. Integrating single-cell transcriptomic data across different conditions, technologies, and species in NATURE BIOTECHNOLOGY
  • 2013-10-06. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position in NATURE METHODS
  • 2021-07-26. Differentiation of exhausted CD8+ T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory in NATURE IMMUNOLOGY
  • <error retrieving object. in <ERROR RETRIEVING OBJECT
  • 2013-05-05. T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion in NATURE IMMUNOLOGY
  • 2019-06-17. TOX is a critical regulator of tumour-specific T cell differentiation in NATURE
  • 2019-02-18. Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade in NATURE IMMUNOLOGY
  • 2017-01-23. Single-cell mRNA quantification and differential analysis with Census in NATURE METHODS
  • 2016-08-02. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy in NATURE
  • 2016-08-02. Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection in NATURE
  • 2019-06-17. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection in NATURE
  • 2019-06-17. Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection in NATURE IMMUNOLOGY
  • 2005-12-28. Restoring function in exhausted CD8 T cells during chronic viral infection in NATURE
  • 2021-07-26. Epigenetic scars of CD8+ T cell exhaustion persist after cure of chronic infection in humans in NATURE IMMUNOLOGY
  • 2010-05-02. GREAT improves functional interpretation of cis-regulatory regions in NATURE BIOTECHNOLOGY
  • 2021-01-04. Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection in NATURE IMMUNOLOGY
  • 2017-05-03. TCF1+ hepatitis C virus-specific CD8+ T cells are maintained after cessation of chronic antigen stimulation in NATURE COMMUNICATIONS
  • 2019-04-03. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets in NATURE COMMUNICATIONS
  • 2012-10-19. Transcriptional control of effector and memory CD8+ T cell differentiation in NATURE REVIEWS IMMUNOLOGY
  • 2016-03-24. Visualizing Genomic Data Using Gviz and Bioconductor in STATISTICAL GENOMICS
  • 2017-05-17. Chromatin states define tumour-specific T cell dysfunction and reprogramming in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41590-021-00975-5

    DOI

    http://dx.doi.org/10.1038/s41590-021-00975-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1139927264

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34312545


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1107", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Immunology", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antigens, Viral", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "CD8-Positive T-Lymphocytes", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Differentiation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Chlorocebus aethiops", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cricetinae", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Epigenesis, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Hepatocyte Nuclear Factor 1-alpha", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Immunologic Memory", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Lymphocytic Choriomeningitis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Lymphocytic choriomeningitis virus", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice, Inbred C57BL", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice, Transgenic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Vero Cells", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt", 
              "id": "http://www.grid.ac/institutes/grid.7776.1", 
              "name": [
                "Department 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 Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Abdel-Hakeem", 
            "givenName": "Mohamed S.", 
            "id": "sg:person.01203111137.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01203111137.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department 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"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Manne", 
            "givenName": "Sasikanth", 
            "id": "sg:person.01257513522.39", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257513522.39"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department 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 at University of Pennsylvania, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Beltra", 
            "givenName": "Jean-Christophe", 
            "id": "sg:person.01255120237.32", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255120237.32"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Microbiology and Immunology, University of Miami, Miami, FL, USA", 
              "id": "http://www.grid.ac/institutes/grid.26790.3a", 
              "name": [
                "Department 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 Microbiology and Immunology, University of Miami, Miami, FL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Stelekati", 
            "givenName": "Erietta", 
            "id": "sg:person.0777421364.38", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0777421364.38"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department 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"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chen", 
            "givenName": "Zeyu", 
            "id": "sg:person.016646712067.72", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016646712067.72"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department 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"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Nzingha", 
            "givenName": "Kito", 
            "id": "sg:person.01162644471.33", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01162644471.33"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department 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"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ali", 
            "givenName": "Mohammed-Alkhatim", 
            "id": "sg:person.01344564444.53", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01344564444.53"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
                "Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Johnson", 
            "givenName": "John L.", 
            "id": "sg:person.01026041103.54", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01026041103.54"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department 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 at University of Pennsylvania, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Giles", 
            "givenName": "Josephine R.", 
            "id": "sg:person.016572206727.12", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016572206727.12"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department 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"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mathew", 
            "givenName": "Divij", 
            "id": "sg:person.01012320561.24", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01012320561.24"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department 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"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Greenplate", 
            "givenName": "Allison R.", 
            "id": "sg:person.0706624752.27", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0706624752.27"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
                "Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA", 
                "Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Vahedi", 
            "givenName": "Golnaz", 
            "id": "sg:person.01075416456.33", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01075416456.33"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department 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 at University of Pennsylvania, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wherry", 
            "givenName": "E. John", 
            "id": "sg:person.0651713732.38", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0651713732.38"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/s41586-019-1326-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1117287858", 
              "https://doi.org/10.1038/s41586-019-1326-9"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ni.2606", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017535009", 
              "https://doi.org/10.1038/ni.2606"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature19330", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006752445", 
              "https://doi.org/10.1038/nature19330"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41590-021-00982-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1139927539", 
              "https://doi.org/10.1038/s41590-021-00982-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nri3307", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016124947", 
              "https://doi.org/10.1038/nri3307"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.2688", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020615304", 
              "https://doi.org/10.1038/nmeth.2688"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41586-019-1324-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1117297772", 
              "https://doi.org/10.1038/s41586-019-1324-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41590-019-0403-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1117297814", 
              "https://doi.org/10.1038/s41590-019-0403-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature22367", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085428066", 
              "https://doi.org/10.1038/nature22367"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.4096", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101885942", 
              "https://doi.org/10.1038/nbt.4096"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-1-4939-3578-9_16", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000858532", 
              "https://doi.org/10.1007/978-1-4939-3578-9_16"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41590-019-0312-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1112199007", 
              "https://doi.org/10.1038/s41590-019-0312-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41467-019-09234-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1113182121", 
              "https://doi.org/10.1038/s41467-019-09234-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature19317", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023763572", 
              "https://doi.org/10.1038/nature19317"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature04444", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018989545", 
              "https://doi.org/10.1038/nature04444"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41590-021-00979-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1139927097", 
              "https://doi.org/10.1038/s41590-021-00979-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41586-019-1325-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1117297771", 
              "https://doi.org/10.1038/s41586-019-1325-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms15050", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085120333", 
              "https://doi.org/10.1038/ncomms15050"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41590-020-00817-w", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1134290884", 
              "https://doi.org/10.1038/s41590-020-00817-w"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.1630", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023421025", 
              "https://doi.org/10.1038/nbt.1630"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.4150", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1074190462", 
              "https://doi.org/10.1038/nmeth.4150"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2021-07-26", 
        "datePublishedReg": "2021-07-26", 
        "description": "Exhausted CD8 T cells (TEX) are a distinct state of T cell differentiation associated with failure to clear chronic viruses and cancer. Immunotherapies such as PD-1 blockade can reinvigorate TEX cells, but reinvigoration is not durable. A major unanswered question is whether TEX cells differentiate into functional durable memory T cells (TMEM) upon antigen clearance. Here, using a mouse model, we found that upon eliminating chronic antigenic stimulation, TEX cells partially (re)acquire phenotypic and transcriptional features of TMEM cells. These \u2018recovering\u2019 TEX cells originated from the T cell factor (TCF-1+) TEX progenitor subset. Nevertheless, the recall capacity of these recovering TEX cells remained compromised as compared to TMEM cells. Chromatin-accessibility profiling revealed a failure to recover core memory epigenetic circuits and maintenance of a largely exhausted open chromatin landscape. Thus, despite some phenotypic and transcriptional recovery upon antigen clearance, exhaustion leaves durable epigenetic scars constraining future immune responses. These results support epigenetic remodeling interventions for TEX cell\u2013targeted immunotherapies.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41590-021-00975-5", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.3932370", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.7029328", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2682480", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2695836", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.3801353", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.9412064", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.3936060", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.4055001", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1022778", 
            "issn": [
              "1529-2908", 
              "1529-2916"
            ], 
            "name": "Nature Immunology", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "8", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "22"
          }
        ], 
        "keywords": [
          "Tmem cells", 
          "open chromatin landscape", 
          "chromatin accessibility profiling", 
          "Tex cells", 
          "chronic antigenic stimulation", 
          "epigenetic circuits", 
          "chromatin landscape", 
          "transcriptional recovery", 
          "T cells", 
          "transcriptional features", 
          "antigen clearance", 
          "major unanswered question", 
          "cell differentiation", 
          "antigenic stimulation", 
          "progenitor subsets", 
          "T cell differentiation", 
          "exhausted CD8 T cells", 
          "PD-1 blockade", 
          "CD8 T cells", 
          "exhausted T cells", 
          "memory T cells", 
          "future immune response", 
          "cells", 
          "differentiation", 
          "memory differentiation", 
          "chronic viruses", 
          "immune response", 
          "mouse model", 
          "distinct states", 
          "immunotherapy", 
          "unanswered questions", 
          "phenotypic", 
          "clearance", 
          "profiling", 
          "stimulation", 
          "recall capacity", 
          "failure", 
          "blockade", 
          "landscape", 
          "scarring", 
          "cancer", 
          "maintenance", 
          "virus", 
          "intervention", 
          "scar", 
          "response", 
          "exhaustion", 
          "subset", 
          "recovery", 
          "capacity", 
          "features", 
          "results", 
          "questions", 
          "state", 
          "model", 
          "reinvigoration", 
          "circuit"
        ], 
        "name": "Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation", 
        "pagination": "1008-1019", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1139927264"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41590-021-00975-5"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "34312545"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41590-021-00975-5", 
          "https://app.dimensions.ai/details/publication/pub.1139927264"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-11-24T21:07", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221124/entities/gbq_results/article/article_874.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41590-021-00975-5"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41590-021-00975-5'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41590-021-00975-5'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41590-021-00975-5'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41590-021-00975-5'


     

    This table displays all metadata directly associated to this object as RDF triples.

    392 TRIPLES      21 PREDICATES      121 URIs      92 LITERALS      25 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41590-021-00975-5 schema:about N0752cb8dc96b4639a321e4d3b73edff8
    2 N0a974f458e8441ab9ca8a140af1b186e
    3 N1ad6e1d3907e48d3ae36a5ab2776b623
    4 N1b6c489716ca496dbfa88c8f813baf98
    5 N20680cc3cf9d44328090f0c4c9ae0572
    6 N3475156251ef4a9d810eb0634c174e36
    7 N35f08f7e522f40e9ba6381a3d5cd3571
    8 N382cf7e9e75148aa9139b9ef3a6bc044
    9 N437e11987d414bd3a06301d78a6f6065
    10 N7b3d4c6c0dd846bea529a5f72d3ca5c7
    11 Na8bf9ea1994744daa278a02a20079e5a
    12 Nb1127a2d53f74f7a9995b6ff2c652d31
    13 Nbafb028cc6994629ac45123e384258e2
    14 Nbed20276ab3846c784639eb66f77c466
    15 Nc3b9dc9fd6304742a5a82ea099a92260
    16 Ne4c331b789e84fa8b32a3edd360bdb97
    17 Nf2f5202fc9ac42dca82c9d0f24f993c2
    18 Nf93783636f194a6f88ff5ef841113921
    19 anzsrc-for:11
    20 anzsrc-for:1107
    21 schema:author N774fc89cf9574d658f403e4f8be1614f
    22 schema:citation sg:pub.10.1007/978-1-4939-3578-9_16
    23 sg:pub.10.1038/nature04444
    24 sg:pub.10.1038/nature19317
    25 sg:pub.10.1038/nature19330
    26 sg:pub.10.1038/nature22367
    27 sg:pub.10.1038/nbt.1630
    28 sg:pub.10.1038/nbt.4096
    29 sg:pub.10.1038/ncomms15050
    30 sg:pub.10.1038/ni.2606
    31 sg:pub.10.1038/nmeth.2688
    32 sg:pub.10.1038/nmeth.4150
    33 sg:pub.10.1038/nri3307
    34 sg:pub.10.1038/s41467-019-09234-6
    35 sg:pub.10.1038/s41586-019-1324-y
    36 sg:pub.10.1038/s41586-019-1325-x
    37 sg:pub.10.1038/s41586-019-1326-9
    38 sg:pub.10.1038/s41590-019-0312-6
    39 sg:pub.10.1038/s41590-019-0403-4
    40 sg:pub.10.1038/s41590-020-00817-w
    41 sg:pub.10.1038/s41590-021-00979-1
    42 sg:pub.10.1038/s41590-021-00982-6
    43 schema:datePublished 2021-07-26
    44 schema:datePublishedReg 2021-07-26
    45 schema:description Exhausted CD8 T cells (TEX) are a distinct state of T cell differentiation associated with failure to clear chronic viruses and cancer. Immunotherapies such as PD-1 blockade can reinvigorate TEX cells, but reinvigoration is not durable. A major unanswered question is whether TEX cells differentiate into functional durable memory T cells (TMEM) upon antigen clearance. Here, using a mouse model, we found that upon eliminating chronic antigenic stimulation, TEX cells partially (re)acquire phenotypic and transcriptional features of TMEM cells. These ‘recovering’ TEX cells originated from the T cell factor (TCF-1+) TEX progenitor subset. Nevertheless, the recall capacity of these recovering TEX cells remained compromised as compared to TMEM cells. Chromatin-accessibility profiling revealed a failure to recover core memory epigenetic circuits and maintenance of a largely exhausted open chromatin landscape. Thus, despite some phenotypic and transcriptional recovery upon antigen clearance, exhaustion leaves durable epigenetic scars constraining future immune responses. These results support epigenetic remodeling interventions for TEX cell–targeted immunotherapies.
    46 schema:genre article
    47 schema:isAccessibleForFree true
    48 schema:isPartOf N0a492457db5b4f1282b9cfaa3940b33f
    49 Nc0883d66a23c4d68906df5eb924c9b93
    50 sg:journal.1022778
    51 schema:keywords CD8 T cells
    52 PD-1 blockade
    53 T cell differentiation
    54 T cells
    55 Tex cells
    56 Tmem cells
    57 antigen clearance
    58 antigenic stimulation
    59 blockade
    60 cancer
    61 capacity
    62 cell differentiation
    63 cells
    64 chromatin accessibility profiling
    65 chromatin landscape
    66 chronic antigenic stimulation
    67 chronic viruses
    68 circuit
    69 clearance
    70 differentiation
    71 distinct states
    72 epigenetic circuits
    73 exhausted CD8 T cells
    74 exhausted T cells
    75 exhaustion
    76 failure
    77 features
    78 future immune response
    79 immune response
    80 immunotherapy
    81 intervention
    82 landscape
    83 maintenance
    84 major unanswered question
    85 memory T cells
    86 memory differentiation
    87 model
    88 mouse model
    89 open chromatin landscape
    90 phenotypic
    91 profiling
    92 progenitor subsets
    93 questions
    94 recall capacity
    95 recovery
    96 reinvigoration
    97 response
    98 results
    99 scar
    100 scarring
    101 state
    102 stimulation
    103 subset
    104 transcriptional features
    105 transcriptional recovery
    106 unanswered questions
    107 virus
    108 schema:name Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation
    109 schema:pagination 1008-1019
    110 schema:productId N4c37954fb21e413b95677139bc105039
    111 N6a91286a92e9415e87e12ee821739451
    112 Nfcd383908d5c42ae992e816097bd3a5f
    113 schema:sameAs https://app.dimensions.ai/details/publication/pub.1139927264
    114 https://doi.org/10.1038/s41590-021-00975-5
    115 schema:sdDatePublished 2022-11-24T21:07
    116 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    117 schema:sdPublisher N3c27ead6c189432089dbf2bbb25bec8a
    118 schema:url https://doi.org/10.1038/s41590-021-00975-5
    119 sgo:license sg:explorer/license/
    120 sgo:sdDataset articles
    121 rdf:type schema:ScholarlyArticle
    122 N0752cb8dc96b4639a321e4d3b73edff8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    123 schema:name Mice
    124 rdf:type schema:DefinedTerm
    125 N0a492457db5b4f1282b9cfaa3940b33f schema:issueNumber 8
    126 rdf:type schema:PublicationIssue
    127 N0a974f458e8441ab9ca8a140af1b186e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    128 schema:name Transcription, Genetic
    129 rdf:type schema:DefinedTerm
    130 N11d0e914a0224fde9955235b1aa9aa62 rdf:first sg:person.0651713732.38
    131 rdf:rest rdf:nil
    132 N17a955ea583d46b5b4e3763783dd4fa2 rdf:first sg:person.01257513522.39
    133 rdf:rest Ne9c619d8a6b1457a885b28ed2fe6dfab
    134 N1ad6e1d3907e48d3ae36a5ab2776b623 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    135 schema:name Lymphocytic choriomeningitis virus
    136 rdf:type schema:DefinedTerm
    137 N1b6c489716ca496dbfa88c8f813baf98 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    138 schema:name Immunologic Memory
    139 rdf:type schema:DefinedTerm
    140 N20680cc3cf9d44328090f0c4c9ae0572 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    141 schema:name CD8-Positive T-Lymphocytes
    142 rdf:type schema:DefinedTerm
    143 N3475156251ef4a9d810eb0634c174e36 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    144 schema:name Epigenesis, Genetic
    145 rdf:type schema:DefinedTerm
    146 N35f08f7e522f40e9ba6381a3d5cd3571 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    147 schema:name Hepatocyte Nuclear Factor 1-alpha
    148 rdf:type schema:DefinedTerm
    149 N382cf7e9e75148aa9139b9ef3a6bc044 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    150 schema:name Lymphocytic Choriomeningitis
    151 rdf:type schema:DefinedTerm
    152 N3b0bc0cd928a4b52abda767a1ac31a4a rdf:first sg:person.016646712067.72
    153 rdf:rest Nfbe4304b94f24179b4efc19a08e15e0c
    154 N3c27ead6c189432089dbf2bbb25bec8a schema:name Springer Nature - SN SciGraph project
    155 rdf:type schema:Organization
    156 N437e11987d414bd3a06301d78a6f6065 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    157 schema:name Chlorocebus aethiops
    158 rdf:type schema:DefinedTerm
    159 N4b06564643844ee080067797b2357e7f rdf:first sg:person.01075416456.33
    160 rdf:rest N11d0e914a0224fde9955235b1aa9aa62
    161 N4c37954fb21e413b95677139bc105039 schema:name dimensions_id
    162 schema:value pub.1139927264
    163 rdf:type schema:PropertyValue
    164 N5829412da40c44fa9849a7f5cadb54ad rdf:first sg:person.01344564444.53
    165 rdf:rest Nb329e03e025b42afa3eb705f4612e103
    166 N606029b578d5427f80c223b4086fbe4a rdf:first sg:person.0706624752.27
    167 rdf:rest N4b06564643844ee080067797b2357e7f
    168 N6a91286a92e9415e87e12ee821739451 schema:name pubmed_id
    169 schema:value 34312545
    170 rdf:type schema:PropertyValue
    171 N774fc89cf9574d658f403e4f8be1614f rdf:first sg:person.01203111137.14
    172 rdf:rest N17a955ea583d46b5b4e3763783dd4fa2
    173 N7b3d4c6c0dd846bea529a5f72d3ca5c7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    174 schema:name Animals
    175 rdf:type schema:DefinedTerm
    176 N7d37d60d09bb458c88fe9ab3dd850c12 rdf:first sg:person.0777421364.38
    177 rdf:rest N3b0bc0cd928a4b52abda767a1ac31a4a
    178 N89d1236033e44da387acaf573ab2d559 rdf:first sg:person.016572206727.12
    179 rdf:rest Na3e47a2c39564d8e9fdd7a606179f7be
    180 Na3e47a2c39564d8e9fdd7a606179f7be rdf:first sg:person.01012320561.24
    181 rdf:rest N606029b578d5427f80c223b4086fbe4a
    182 Na8bf9ea1994744daa278a02a20079e5a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    183 schema:name Cricetinae
    184 rdf:type schema:DefinedTerm
    185 Nb1127a2d53f74f7a9995b6ff2c652d31 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    186 schema:name Mice, Inbred C57BL
    187 rdf:type schema:DefinedTerm
    188 Nb329e03e025b42afa3eb705f4612e103 rdf:first sg:person.01026041103.54
    189 rdf:rest N89d1236033e44da387acaf573ab2d559
    190 Nbafb028cc6994629ac45123e384258e2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    191 schema:name Female
    192 rdf:type schema:DefinedTerm
    193 Nbed20276ab3846c784639eb66f77c466 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    194 schema:name Cell Differentiation
    195 rdf:type schema:DefinedTerm
    196 Nc0883d66a23c4d68906df5eb924c9b93 schema:volumeNumber 22
    197 rdf:type schema:PublicationVolume
    198 Nc3b9dc9fd6304742a5a82ea099a92260 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    199 schema:name Vero Cells
    200 rdf:type schema:DefinedTerm
    201 Ne4c331b789e84fa8b32a3edd360bdb97 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    202 schema:name Mice, Transgenic
    203 rdf:type schema:DefinedTerm
    204 Ne9c619d8a6b1457a885b28ed2fe6dfab rdf:first sg:person.01255120237.32
    205 rdf:rest N7d37d60d09bb458c88fe9ab3dd850c12
    206 Nf2f5202fc9ac42dca82c9d0f24f993c2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    207 schema:name Antigens, Viral
    208 rdf:type schema:DefinedTerm
    209 Nf93783636f194a6f88ff5ef841113921 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    210 schema:name Cell Line
    211 rdf:type schema:DefinedTerm
    212 Nfbe4304b94f24179b4efc19a08e15e0c rdf:first sg:person.01162644471.33
    213 rdf:rest N5829412da40c44fa9849a7f5cadb54ad
    214 Nfcd383908d5c42ae992e816097bd3a5f schema:name doi
    215 schema:value 10.1038/s41590-021-00975-5
    216 rdf:type schema:PropertyValue
    217 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    218 schema:name Medical and Health Sciences
    219 rdf:type schema:DefinedTerm
    220 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
    221 schema:name Immunology
    222 rdf:type schema:DefinedTerm
    223 sg:grant.2682480 http://pending.schema.org/fundedItem sg:pub.10.1038/s41590-021-00975-5
    224 rdf:type schema:MonetaryGrant
    225 sg:grant.2695836 http://pending.schema.org/fundedItem sg:pub.10.1038/s41590-021-00975-5
    226 rdf:type schema:MonetaryGrant
    227 sg:grant.3801353 http://pending.schema.org/fundedItem sg:pub.10.1038/s41590-021-00975-5
    228 rdf:type schema:MonetaryGrant
    229 sg:grant.3932370 http://pending.schema.org/fundedItem sg:pub.10.1038/s41590-021-00975-5
    230 rdf:type schema:MonetaryGrant
    231 sg:grant.3936060 http://pending.schema.org/fundedItem sg:pub.10.1038/s41590-021-00975-5
    232 rdf:type schema:MonetaryGrant
    233 sg:grant.4055001 http://pending.schema.org/fundedItem sg:pub.10.1038/s41590-021-00975-5
    234 rdf:type schema:MonetaryGrant
    235 sg:grant.7029328 http://pending.schema.org/fundedItem sg:pub.10.1038/s41590-021-00975-5
    236 rdf:type schema:MonetaryGrant
    237 sg:grant.9412064 http://pending.schema.org/fundedItem sg:pub.10.1038/s41590-021-00975-5
    238 rdf:type schema:MonetaryGrant
    239 sg:journal.1022778 schema:issn 1529-2908
    240 1529-2916
    241 schema:name Nature Immunology
    242 schema:publisher Springer Nature
    243 rdf:type schema:Periodical
    244 sg:person.01012320561.24 schema:affiliation grid-institutes:grid.25879.31
    245 schema:familyName Mathew
    246 schema:givenName Divij
    247 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01012320561.24
    248 rdf:type schema:Person
    249 sg:person.01026041103.54 schema:affiliation grid-institutes:grid.25879.31
    250 schema:familyName Johnson
    251 schema:givenName John L.
    252 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01026041103.54
    253 rdf:type schema:Person
    254 sg:person.01075416456.33 schema:affiliation grid-institutes:grid.25879.31
    255 schema:familyName Vahedi
    256 schema:givenName Golnaz
    257 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01075416456.33
    258 rdf:type schema:Person
    259 sg:person.01162644471.33 schema:affiliation grid-institutes:grid.25879.31
    260 schema:familyName Nzingha
    261 schema:givenName Kito
    262 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01162644471.33
    263 rdf:type schema:Person
    264 sg:person.01203111137.14 schema:affiliation grid-institutes:grid.7776.1
    265 schema:familyName Abdel-Hakeem
    266 schema:givenName Mohamed S.
    267 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01203111137.14
    268 rdf:type schema:Person
    269 sg:person.01255120237.32 schema:affiliation grid-institutes:grid.25879.31
    270 schema:familyName Beltra
    271 schema:givenName Jean-Christophe
    272 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255120237.32
    273 rdf:type schema:Person
    274 sg:person.01257513522.39 schema:affiliation grid-institutes:grid.25879.31
    275 schema:familyName Manne
    276 schema:givenName Sasikanth
    277 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257513522.39
    278 rdf:type schema:Person
    279 sg:person.01344564444.53 schema:affiliation grid-institutes:grid.25879.31
    280 schema:familyName Ali
    281 schema:givenName Mohammed-Alkhatim
    282 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01344564444.53
    283 rdf:type schema:Person
    284 sg:person.016572206727.12 schema:affiliation grid-institutes:grid.25879.31
    285 schema:familyName Giles
    286 schema:givenName Josephine R.
    287 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016572206727.12
    288 rdf:type schema:Person
    289 sg:person.016646712067.72 schema:affiliation grid-institutes:grid.25879.31
    290 schema:familyName Chen
    291 schema:givenName Zeyu
    292 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016646712067.72
    293 rdf:type schema:Person
    294 sg:person.0651713732.38 schema:affiliation grid-institutes:grid.25879.31
    295 schema:familyName Wherry
    296 schema:givenName E. John
    297 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0651713732.38
    298 rdf:type schema:Person
    299 sg:person.0706624752.27 schema:affiliation grid-institutes:grid.25879.31
    300 schema:familyName Greenplate
    301 schema:givenName Allison R.
    302 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0706624752.27
    303 rdf:type schema:Person
    304 sg:person.0777421364.38 schema:affiliation grid-institutes:grid.26790.3a
    305 schema:familyName Stelekati
    306 schema:givenName Erietta
    307 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0777421364.38
    308 rdf:type schema:Person
    309 sg:pub.10.1007/978-1-4939-3578-9_16 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000858532
    310 https://doi.org/10.1007/978-1-4939-3578-9_16
    311 rdf:type schema:CreativeWork
    312 sg:pub.10.1038/nature04444 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018989545
    313 https://doi.org/10.1038/nature04444
    314 rdf:type schema:CreativeWork
    315 sg:pub.10.1038/nature19317 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023763572
    316 https://doi.org/10.1038/nature19317
    317 rdf:type schema:CreativeWork
    318 sg:pub.10.1038/nature19330 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006752445
    319 https://doi.org/10.1038/nature19330
    320 rdf:type schema:CreativeWork
    321 sg:pub.10.1038/nature22367 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085428066
    322 https://doi.org/10.1038/nature22367
    323 rdf:type schema:CreativeWork
    324 sg:pub.10.1038/nbt.1630 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023421025
    325 https://doi.org/10.1038/nbt.1630
    326 rdf:type schema:CreativeWork
    327 sg:pub.10.1038/nbt.4096 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101885942
    328 https://doi.org/10.1038/nbt.4096
    329 rdf:type schema:CreativeWork
    330 sg:pub.10.1038/ncomms15050 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085120333
    331 https://doi.org/10.1038/ncomms15050
    332 rdf:type schema:CreativeWork
    333 sg:pub.10.1038/ni.2606 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017535009
    334 https://doi.org/10.1038/ni.2606
    335 rdf:type schema:CreativeWork
    336 sg:pub.10.1038/nmeth.2688 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020615304
    337 https://doi.org/10.1038/nmeth.2688
    338 rdf:type schema:CreativeWork
    339 sg:pub.10.1038/nmeth.4150 schema:sameAs https://app.dimensions.ai/details/publication/pub.1074190462
    340 https://doi.org/10.1038/nmeth.4150
    341 rdf:type schema:CreativeWork
    342 sg:pub.10.1038/nri3307 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016124947
    343 https://doi.org/10.1038/nri3307
    344 rdf:type schema:CreativeWork
    345 sg:pub.10.1038/s41467-019-09234-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1113182121
    346 https://doi.org/10.1038/s41467-019-09234-6
    347 rdf:type schema:CreativeWork
    348 sg:pub.10.1038/s41586-019-1324-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1117297772
    349 https://doi.org/10.1038/s41586-019-1324-y
    350 rdf:type schema:CreativeWork
    351 sg:pub.10.1038/s41586-019-1325-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1117297771
    352 https://doi.org/10.1038/s41586-019-1325-x
    353 rdf:type schema:CreativeWork
    354 sg:pub.10.1038/s41586-019-1326-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1117287858
    355 https://doi.org/10.1038/s41586-019-1326-9
    356 rdf:type schema:CreativeWork
    357 sg:pub.10.1038/s41590-019-0312-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112199007
    358 https://doi.org/10.1038/s41590-019-0312-6
    359 rdf:type schema:CreativeWork
    360 sg:pub.10.1038/s41590-019-0403-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1117297814
    361 https://doi.org/10.1038/s41590-019-0403-4
    362 rdf:type schema:CreativeWork
    363 sg:pub.10.1038/s41590-020-00817-w schema:sameAs https://app.dimensions.ai/details/publication/pub.1134290884
    364 https://doi.org/10.1038/s41590-020-00817-w
    365 rdf:type schema:CreativeWork
    366 sg:pub.10.1038/s41590-021-00979-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1139927097
    367 https://doi.org/10.1038/s41590-021-00979-1
    368 rdf:type schema:CreativeWork
    369 sg:pub.10.1038/s41590-021-00982-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1139927539
    370 https://doi.org/10.1038/s41590-021-00982-6
    371 rdf:type schema:CreativeWork
    372 grid-institutes:grid.25879.31 schema:alternateName Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
    373 Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    374 Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA
    375 Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA
    376 schema:name Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA
    377 Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
    378 Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
    379 Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    380 Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA
    381 Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA
    382 rdf:type schema:Organization
    383 grid-institutes:grid.26790.3a schema:alternateName Department of Microbiology and Immunology, University of Miami, Miami, FL, USA
    384 schema:name Department of Microbiology and Immunology, University of Miami, Miami, FL, USA
    385 Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
    386 Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    387 rdf:type schema:Organization
    388 grid-institutes:grid.7776.1 schema:alternateName Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
    389 schema:name Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
    390 Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
    391 Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    392 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...