PD-1 blockade induces responses by inhibiting adaptive immune resistance View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-11

AUTHORS

Paul C. Tumeh, Christina L. Harview, Jennifer H. Yearley, I. Peter Shintaku, Emma J. M. Taylor, Lidia Robert, Bartosz Chmielowski, Marko Spasic, Gina Henry, Voicu Ciobanu, Alisha N. West, Manuel Carmona, Christine Kivork, Elizabeth Seja, Grace Cherry, Antonio J. Gutierrez, Tristan R. Grogan, Christine Mateus, Gorana Tomasic, John A. Glaspy, Ryan O. Emerson, Harlan Robins, Robert H. Pierce, David A. Elashoff, Caroline Robert, Antoni Ribas

ABSTRACT

Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune resistance). Here we show that pre-existing CD8(+) T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analysed samples from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next-generation sequencing for T-cell antigen receptors (TCRs). In serially sampled tumours, patients responding to treatment showed proliferation of intratumoral CD8(+) T cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8-, PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8(+) T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance. More... »

PAGES

568

Journal

TITLE

Nature

ISSUE

7528

VOLUME

515

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature13954

DOI

http://dx.doi.org/10.1038/nature13954

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020455470

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25428505


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/2008/1107", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Immunology", 
        "type": "DefinedTerm"
      }, 
      {
        "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"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adaptive Immunity", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Aged, 80 and over", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Biomarkers", 
        "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 Proliferation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Expression Regulation, Neoplastic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Immunotherapy", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Melanoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Middle Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Models, Biological", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Multivariate Analysis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Programmed Cell Death 1 Receptor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Treatment Outcome", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA", 
            "Jonsson Comprehensive Cancer Center, Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Tumeh", 
        "givenName": "Paul C.", 
        "id": "sg:person.0773374227.51", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0773374227.51"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Harview", 
        "givenName": "Christina L.", 
        "id": "sg:person.01235660650.28", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01235660650.28"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "MSD (United States)", 
          "id": "https://www.grid.ac/institutes/grid.417993.1", 
          "name": [
            "Merck & Co, Palo Alto, California 94304, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yearley", 
        "givenName": "Jennifer H.", 
        "id": "sg:person.01121154113.79", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01121154113.79"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shintaku", 
        "givenName": "I. Peter", 
        "id": "sg:person.012735127714.39", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012735127714.39"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Taylor", 
        "givenName": "Emma J. M.", 
        "id": "sg:person.01141246132.05", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01141246132.05"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Robert", 
        "givenName": "Lidia", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA", 
            "Jonsson Comprehensive Cancer Center, Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chmielowski", 
        "givenName": "Bartosz", 
        "id": "sg:person.01270326576.37", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01270326576.37"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Spasic", 
        "givenName": "Marko", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Henry", 
        "givenName": "Gina", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ciobanu", 
        "givenName": "Voicu", 
        "id": "sg:person.01021121412.07", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01021121412.07"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "West", 
        "givenName": "Alisha N.", 
        "id": "sg:person.0646622272.30", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0646622272.30"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Carmona", 
        "givenName": "Manuel", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kivork", 
        "givenName": "Christine", 
        "id": "sg:person.0751246211.79", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0751246211.79"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Seja", 
        "givenName": "Elizabeth", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cherry", 
        "givenName": "Grace", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gutierrez", 
        "givenName": "Antonio J.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Grogan", 
        "givenName": "Tristan R.", 
        "id": "sg:person.0713510152.12", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0713510152.12"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institut Gustave Roussy", 
          "id": "https://www.grid.ac/institutes/grid.14925.3b", 
          "name": [
            "Gustave Roussy and INSERM U981, Villejuif, Paris Sud, France"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mateus", 
        "givenName": "Christine", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institut Gustave Roussy", 
          "id": "https://www.grid.ac/institutes/grid.14925.3b", 
          "name": [
            "Gustave Roussy and INSERM U981, Villejuif, Paris Sud, France"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Tomasic", 
        "givenName": "Gorana", 
        "id": "sg:person.0665460265.17", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0665460265.17"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA", 
            "Jonsson Comprehensive Cancer Center, Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Glaspy", 
        "givenName": "John A.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Adaptive Biotechnologies (United States)", 
          "id": "https://www.grid.ac/institutes/grid.421940.a", 
          "name": [
            "Adaptive Biotechnologies, Seattle, Washington 98102, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Emerson", 
        "givenName": "Ryan O.", 
        "id": "sg:person.0737320651.15", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0737320651.15"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fred Hutchinson Cancer Research Center", 
          "id": "https://www.grid.ac/institutes/grid.270240.3", 
          "name": [
            "Adaptive Biotechnologies, Seattle, Washington 98102, USA", 
            "Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Robins", 
        "givenName": "Harlan", 
        "id": "sg:person.0661241620.11", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0661241620.11"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "MSD (United States)", 
          "id": "https://www.grid.ac/institutes/grid.417993.1", 
          "name": [
            "Merck & Co, Palo Alto, California 94304, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Pierce", 
        "givenName": "Robert H.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA", 
            "Jonsson Comprehensive Cancer Center, Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Elashoff", 
        "givenName": "David A.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institut Gustave Roussy", 
          "id": "https://www.grid.ac/institutes/grid.14925.3b", 
          "name": [
            "Gustave Roussy and INSERM U981, Villejuif, Paris Sud, France"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Robert", 
        "givenName": "Caroline", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "University of California Los Angeles (UCLA), Los Angeles, California 90095, USA", 
            "Jonsson Comprehensive Cancer Center, Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ribas", 
        "givenName": "Antoni", 
        "id": "sg:person.0627244670.28", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0627244670.28"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-13-3271", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004953031"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0140-6736(14)60958-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012632588"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2009-04-217604", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014830407"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-13-2752", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015640008"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa020177", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017266513"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-13-2797", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018432563"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1129139", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021857158"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa1302369", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024659470"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/scitranslmed.3006504", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027702744"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/2159-8290.cd-13-0458", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028088139"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-09-1624", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028571226"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms3680", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029134323", 
          "https://doi.org/10.1038/ncomms3680"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa051424", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029918763"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm1517", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039360772", 
          "https://doi.org/10.1038/nm1517"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm1517", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039360772", 
          "https://doi.org/10.1038/nm1517"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa1305133", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042841008"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa1200690", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042896583"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2013.49.4757", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045388928"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa1200694", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047413837"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2013.53.0105", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047895673"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc3239", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047946992", 
          "https://doi.org/10.1038/nrc3239"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2014.32.18_suppl.lba9000", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1083398367"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2014-11", 
    "datePublishedReg": "2014-11-01", 
    "description": "Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune resistance). Here we show that pre-existing CD8(+) T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analysed samples from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next-generation sequencing for T-cell antigen receptors (TCRs). In serially sampled tumours, patients responding to treatment showed proliferation of intratumoral CD8(+) T cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8-, PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8(+) T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance. ", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/nature13954", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2410267", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2699040", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2482110", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2705215", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2435886", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2438817", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1018957", 
        "issn": [
          "0090-0028", 
          "1476-4687"
        ], 
        "name": "Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "7528", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "515"
      }
    ], 
    "name": "PD-1 blockade induces responses by inhibiting adaptive immune resistance", 
    "pagination": "568", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "617751d594cd34317f17fe1a38eb806783f8cb8acf8a1e777028558d6ff01732"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "25428505"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "0410462"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/nature13954"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1020455470"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/nature13954", 
      "https://app.dimensions.ai/details/publication/pub.1020455470"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T23:31", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8693_00000550.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/nature13954"
  }
]
 

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/nature13954'

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/nature13954'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature13954'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature13954'


 

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

392 TRIPLES      21 PREDICATES      67 URIs      38 LITERALS      26 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/nature13954 schema:about N06af4619b3be4c3fbb8ee785b948b0dc
2 N095c7daa95e449c0bda487213784970b
3 N0a4829a9e77743d4b317fd466d7b43f6
4 N2802748cc0594b77b1a62b94e57beb7b
5 N2caac3caa22f4461b83ce6c2f4692423
6 N36edf98804bb4e939e921260389965ef
7 N485d189afa914dcd9265a6b3f7b0ac3d
8 N48d12fb3bcb24ec189498bdcfec0b7a6
9 N580d7506e5e54efd9eae4d96c792a9dc
10 N76bf2087060640e989f38918c2a56955
11 N8358ec35bf5e4be18e893787fccb7a54
12 N8b2cde2e74f54e3eae88a3529c672b8b
13 Na11b40d2942a4530b73b0593f6fd489b
14 Nad1961b2fb20402d99a0071dfae704d0
15 Nb442a35e2123409e9ff67c356fb47c86
16 Nbb02b8f0e85c452aac40ba6239aa6d67
17 Nf1473b19af2c4e33a37ec7ef80b75ed5
18 anzsrc-for:11
19 anzsrc-for:1107
20 schema:author Nb0a6c330924149eebfcd593254e0f53f
21 schema:citation sg:pub.10.1038/ncomms3680
22 sg:pub.10.1038/nm1517
23 sg:pub.10.1038/nrc3239
24 https://doi.org/10.1016/s0140-6736(14)60958-2
25 https://doi.org/10.1056/nejmoa020177
26 https://doi.org/10.1056/nejmoa051424
27 https://doi.org/10.1056/nejmoa1200690
28 https://doi.org/10.1056/nejmoa1200694
29 https://doi.org/10.1056/nejmoa1302369
30 https://doi.org/10.1056/nejmoa1305133
31 https://doi.org/10.1126/science.1129139
32 https://doi.org/10.1126/scitranslmed.3006504
33 https://doi.org/10.1158/0008-5472.can-13-2752
34 https://doi.org/10.1158/1078-0432.ccr-09-1624
35 https://doi.org/10.1158/1078-0432.ccr-13-2797
36 https://doi.org/10.1158/1078-0432.ccr-13-3271
37 https://doi.org/10.1158/2159-8290.cd-13-0458
38 https://doi.org/10.1182/blood-2009-04-217604
39 https://doi.org/10.1200/jco.2013.49.4757
40 https://doi.org/10.1200/jco.2013.53.0105
41 https://doi.org/10.1200/jco.2014.32.18_suppl.lba9000
42 schema:datePublished 2014-11
43 schema:datePublishedReg 2014-11-01
44 schema:description Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune resistance). Here we show that pre-existing CD8(+) T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analysed samples from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next-generation sequencing for T-cell antigen receptors (TCRs). In serially sampled tumours, patients responding to treatment showed proliferation of intratumoral CD8(+) T cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8-, PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8(+) T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance.
45 schema:genre research_article
46 schema:inLanguage en
47 schema:isAccessibleForFree true
48 schema:isPartOf N5b3ab3a053174a0b88ae8cde206f40cb
49 Ndafcf09a943c4ebc95c67e5d2940a417
50 sg:journal.1018957
51 schema:name PD-1 blockade induces responses by inhibiting adaptive immune resistance
52 schema:pagination 568
53 schema:productId N30024a35592b43e986b6eb75d2cfd1d8
54 N50e7c22ce62144e0a6367f4fa96973fa
55 N9a15005aced74d1d867d68511b02ef50
56 Naac1571a3bc64d8288e91787d3e0ffc9
57 Ne73f0e5c26f34a7ca6268b699fe9c07f
58 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020455470
59 https://doi.org/10.1038/nature13954
60 schema:sdDatePublished 2019-04-10T23:31
61 schema:sdLicense https://scigraph.springernature.com/explorer/license/
62 schema:sdPublisher Nb96f9371ba7c49068a6f9bad3de9b7bc
63 schema:url https://www.nature.com/articles/nature13954
64 sgo:license sg:explorer/license/
65 sgo:sdDataset articles
66 rdf:type schema:ScholarlyArticle
67 N059c1be3c29045e0a46233391fc79dc3 rdf:first sg:person.0627244670.28
68 rdf:rest rdf:nil
69 N06af4619b3be4c3fbb8ee785b948b0dc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
70 schema:name Melanoma
71 rdf:type schema:DefinedTerm
72 N095c7daa95e449c0bda487213784970b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
73 schema:name Adaptive Immunity
74 rdf:type schema:DefinedTerm
75 N0a17728fd11a4515bdc9f5471bb625db rdf:first sg:person.01270326576.37
76 rdf:rest N43c26dcb199149c89db046cc0a3bd1d0
77 N0a4829a9e77743d4b317fd466d7b43f6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
78 schema:name Cell Proliferation
79 rdf:type schema:DefinedTerm
80 N1a95d81d7a4847a99ec0d4b7f6e15c19 rdf:first Naf341c1f08ca484b932db93d6b32dbc2
81 rdf:rest N97dc919429354506a7dbd4aea1c998e7
82 N2506343020aa4d21aea1ca906b8cab36 schema:affiliation https://www.grid.ac/institutes/grid.14925.3b
83 schema:familyName Robert
84 schema:givenName Caroline
85 rdf:type schema:Person
86 N2802748cc0594b77b1a62b94e57beb7b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
87 schema:name Programmed Cell Death 1 Receptor
88 rdf:type schema:DefinedTerm
89 N2a69ffe273684dcf94855be86bb39c68 rdf:first Nda332f4220a54d9bbc5afd035d9bdb85
90 rdf:rest N2b74b41997c74208bc4cb2315882da51
91 N2a8d896cc21642ada11c509b3b2eaaa9 rdf:first sg:person.01141246132.05
92 rdf:rest N2c36172476a741d589cd4ef91ffc1530
93 N2b399a51c0fb4c40bd9aa040eb00aef4 rdf:first sg:person.0751246211.79
94 rdf:rest N2a69ffe273684dcf94855be86bb39c68
95 N2b74b41997c74208bc4cb2315882da51 rdf:first Nb91dd6eddea4459eb9f5c52673e6ea74
96 rdf:rest N3cc4924cf2bd4989a39fddd8542c0775
97 N2c36172476a741d589cd4ef91ffc1530 rdf:first N347c0d418d124354a7a643469f43a2bb
98 rdf:rest N0a17728fd11a4515bdc9f5471bb625db
99 N2caac3caa22f4461b83ce6c2f4692423 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
100 schema:name CD8-Positive T-Lymphocytes
101 rdf:type schema:DefinedTerm
102 N30024a35592b43e986b6eb75d2cfd1d8 schema:name doi
103 schema:value 10.1038/nature13954
104 rdf:type schema:PropertyValue
105 N347c0d418d124354a7a643469f43a2bb schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
106 schema:familyName Robert
107 schema:givenName Lidia
108 rdf:type schema:Person
109 N36edf98804bb4e939e921260389965ef schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
110 schema:name Biomarkers
111 rdf:type schema:DefinedTerm
112 N382395b6f67a4386a70b44442841ac24 rdf:first N8b4d5746759d4e70a0c1e885e7fbcd89
113 rdf:rest N2b399a51c0fb4c40bd9aa040eb00aef4
114 N3a1c2a379bb94c8f983814a330b4a60a schema:affiliation https://www.grid.ac/institutes/grid.417993.1
115 schema:familyName Pierce
116 schema:givenName Robert H.
117 rdf:type schema:Person
118 N3cc4924cf2bd4989a39fddd8542c0775 rdf:first N954a3b2aa35e48458d12ffdf4cd1a0f8
119 rdf:rest N66b3a6fbb8cd419b9319ebf140111a7f
120 N3f88cbcf411c4d12837f03ef77d18f2e rdf:first sg:person.01121154113.79
121 rdf:rest N9023388fbe0346b39f154c891f3e7b96
122 N43c26dcb199149c89db046cc0a3bd1d0 rdf:first Nfb215b5f52964de88ebe55779a24ec30
123 rdf:rest N4bf7ea9fb0364beda1424542031c0a5c
124 N485d189afa914dcd9265a6b3f7b0ac3d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
125 schema:name Aged
126 rdf:type schema:DefinedTerm
127 N48d12fb3bcb24ec189498bdcfec0b7a6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name Gene Expression Regulation, Neoplastic
129 rdf:type schema:DefinedTerm
130 N4bf7ea9fb0364beda1424542031c0a5c rdf:first Ne5d9b377afd546aba2b0fce72abf6039
131 rdf:rest N73237bfe0bfa40248d9210eec011cc6b
132 N4c276521e3054666b4b653fa35ce6770 rdf:first sg:person.01235660650.28
133 rdf:rest N3f88cbcf411c4d12837f03ef77d18f2e
134 N50e7c22ce62144e0a6367f4fa96973fa schema:name dimensions_id
135 schema:value pub.1020455470
136 rdf:type schema:PropertyValue
137 N580d7506e5e54efd9eae4d96c792a9dc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
138 schema:name Middle Aged
139 rdf:type schema:DefinedTerm
140 N5b3ab3a053174a0b88ae8cde206f40cb schema:issueNumber 7528
141 rdf:type schema:PublicationIssue
142 N66b3a6fbb8cd419b9319ebf140111a7f rdf:first sg:person.0713510152.12
143 rdf:rest Na84664a13f23485b8d9cb4306e9d5a0e
144 N73237bfe0bfa40248d9210eec011cc6b rdf:first sg:person.01021121412.07
145 rdf:rest Nb3e496e4866d4331aff16491fe29a9ec
146 N76bf2087060640e989f38918c2a56955 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
147 schema:name Humans
148 rdf:type schema:DefinedTerm
149 N7c3d970d48da458bbfb3f431c191c434 rdf:first sg:person.0665460265.17
150 rdf:rest N1a95d81d7a4847a99ec0d4b7f6e15c19
151 N8358ec35bf5e4be18e893787fccb7a54 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
152 schema:name Immunotherapy
153 rdf:type schema:DefinedTerm
154 N8b2cde2e74f54e3eae88a3529c672b8b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
155 schema:name Female
156 rdf:type schema:DefinedTerm
157 N8b4d5746759d4e70a0c1e885e7fbcd89 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
158 schema:familyName Carmona
159 schema:givenName Manuel
160 rdf:type schema:Person
161 N8ce457c5770c4313b1b68d54414c2a58 rdf:first Nc3a91e9cfac04123a5d54b66750025e5
162 rdf:rest Na746e7471aa744f08d29775a4d4daefa
163 N9023388fbe0346b39f154c891f3e7b96 rdf:first sg:person.012735127714.39
164 rdf:rest N2a8d896cc21642ada11c509b3b2eaaa9
165 N9440e4ae884b4e10bc8639764f1315bb rdf:first sg:person.0661241620.11
166 rdf:rest Nea52acaf21884965b0cc6c8c79f02ae3
167 N954a3b2aa35e48458d12ffdf4cd1a0f8 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
168 schema:familyName Gutierrez
169 schema:givenName Antonio J.
170 rdf:type schema:Person
171 N97dc919429354506a7dbd4aea1c998e7 rdf:first sg:person.0737320651.15
172 rdf:rest N9440e4ae884b4e10bc8639764f1315bb
173 N9a15005aced74d1d867d68511b02ef50 schema:name nlm_unique_id
174 schema:value 0410462
175 rdf:type schema:PropertyValue
176 Na11b40d2942a4530b73b0593f6fd489b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
177 schema:name Models, Biological
178 rdf:type schema:DefinedTerm
179 Na746e7471aa744f08d29775a4d4daefa rdf:first N2506343020aa4d21aea1ca906b8cab36
180 rdf:rest N059c1be3c29045e0a46233391fc79dc3
181 Na84664a13f23485b8d9cb4306e9d5a0e rdf:first Nf7c4d17a538448dea653abb0b78647c7
182 rdf:rest N7c3d970d48da458bbfb3f431c191c434
183 Naac1571a3bc64d8288e91787d3e0ffc9 schema:name pubmed_id
184 schema:value 25428505
185 rdf:type schema:PropertyValue
186 Nad1961b2fb20402d99a0071dfae704d0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
187 schema:name Treatment Outcome
188 rdf:type schema:DefinedTerm
189 Naf341c1f08ca484b932db93d6b32dbc2 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
190 schema:familyName Glaspy
191 schema:givenName John A.
192 rdf:type schema:Person
193 Nb0a6c330924149eebfcd593254e0f53f rdf:first sg:person.0773374227.51
194 rdf:rest N4c276521e3054666b4b653fa35ce6770
195 Nb3e496e4866d4331aff16491fe29a9ec rdf:first sg:person.0646622272.30
196 rdf:rest N382395b6f67a4386a70b44442841ac24
197 Nb442a35e2123409e9ff67c356fb47c86 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
198 schema:name Multivariate Analysis
199 rdf:type schema:DefinedTerm
200 Nb91dd6eddea4459eb9f5c52673e6ea74 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
201 schema:familyName Cherry
202 schema:givenName Grace
203 rdf:type schema:Person
204 Nb96f9371ba7c49068a6f9bad3de9b7bc schema:name Springer Nature - SN SciGraph project
205 rdf:type schema:Organization
206 Nbb02b8f0e85c452aac40ba6239aa6d67 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
207 schema:name Male
208 rdf:type schema:DefinedTerm
209 Nc3a91e9cfac04123a5d54b66750025e5 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
210 schema:familyName Elashoff
211 schema:givenName David A.
212 rdf:type schema:Person
213 Nda332f4220a54d9bbc5afd035d9bdb85 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
214 schema:familyName Seja
215 schema:givenName Elizabeth
216 rdf:type schema:Person
217 Ndafcf09a943c4ebc95c67e5d2940a417 schema:volumeNumber 515
218 rdf:type schema:PublicationVolume
219 Ne5d9b377afd546aba2b0fce72abf6039 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
220 schema:familyName Henry
221 schema:givenName Gina
222 rdf:type schema:Person
223 Ne73f0e5c26f34a7ca6268b699fe9c07f schema:name readcube_id
224 schema:value 617751d594cd34317f17fe1a38eb806783f8cb8acf8a1e777028558d6ff01732
225 rdf:type schema:PropertyValue
226 Nea52acaf21884965b0cc6c8c79f02ae3 rdf:first N3a1c2a379bb94c8f983814a330b4a60a
227 rdf:rest N8ce457c5770c4313b1b68d54414c2a58
228 Nf1473b19af2c4e33a37ec7ef80b75ed5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
229 schema:name Aged, 80 and over
230 rdf:type schema:DefinedTerm
231 Nf7c4d17a538448dea653abb0b78647c7 schema:affiliation https://www.grid.ac/institutes/grid.14925.3b
232 schema:familyName Mateus
233 schema:givenName Christine
234 rdf:type schema:Person
235 Nfb215b5f52964de88ebe55779a24ec30 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
236 schema:familyName Spasic
237 schema:givenName Marko
238 rdf:type schema:Person
239 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
240 schema:name Medical and Health Sciences
241 rdf:type schema:DefinedTerm
242 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
243 schema:name Immunology
244 rdf:type schema:DefinedTerm
245 sg:grant.2410267 http://pending.schema.org/fundedItem sg:pub.10.1038/nature13954
246 rdf:type schema:MonetaryGrant
247 sg:grant.2435886 http://pending.schema.org/fundedItem sg:pub.10.1038/nature13954
248 rdf:type schema:MonetaryGrant
249 sg:grant.2438817 http://pending.schema.org/fundedItem sg:pub.10.1038/nature13954
250 rdf:type schema:MonetaryGrant
251 sg:grant.2482110 http://pending.schema.org/fundedItem sg:pub.10.1038/nature13954
252 rdf:type schema:MonetaryGrant
253 sg:grant.2699040 http://pending.schema.org/fundedItem sg:pub.10.1038/nature13954
254 rdf:type schema:MonetaryGrant
255 sg:grant.2705215 http://pending.schema.org/fundedItem sg:pub.10.1038/nature13954
256 rdf:type schema:MonetaryGrant
257 sg:journal.1018957 schema:issn 0090-0028
258 1476-4687
259 schema:name Nature
260 rdf:type schema:Periodical
261 sg:person.01021121412.07 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
262 schema:familyName Ciobanu
263 schema:givenName Voicu
264 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01021121412.07
265 rdf:type schema:Person
266 sg:person.01121154113.79 schema:affiliation https://www.grid.ac/institutes/grid.417993.1
267 schema:familyName Yearley
268 schema:givenName Jennifer H.
269 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01121154113.79
270 rdf:type schema:Person
271 sg:person.01141246132.05 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
272 schema:familyName Taylor
273 schema:givenName Emma J. M.
274 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01141246132.05
275 rdf:type schema:Person
276 sg:person.01235660650.28 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
277 schema:familyName Harview
278 schema:givenName Christina L.
279 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01235660650.28
280 rdf:type schema:Person
281 sg:person.01270326576.37 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
282 schema:familyName Chmielowski
283 schema:givenName Bartosz
284 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01270326576.37
285 rdf:type schema:Person
286 sg:person.012735127714.39 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
287 schema:familyName Shintaku
288 schema:givenName I. Peter
289 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012735127714.39
290 rdf:type schema:Person
291 sg:person.0627244670.28 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
292 schema:familyName Ribas
293 schema:givenName Antoni
294 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0627244670.28
295 rdf:type schema:Person
296 sg:person.0646622272.30 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
297 schema:familyName West
298 schema:givenName Alisha N.
299 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0646622272.30
300 rdf:type schema:Person
301 sg:person.0661241620.11 schema:affiliation https://www.grid.ac/institutes/grid.270240.3
302 schema:familyName Robins
303 schema:givenName Harlan
304 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0661241620.11
305 rdf:type schema:Person
306 sg:person.0665460265.17 schema:affiliation https://www.grid.ac/institutes/grid.14925.3b
307 schema:familyName Tomasic
308 schema:givenName Gorana
309 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0665460265.17
310 rdf:type schema:Person
311 sg:person.0713510152.12 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
312 schema:familyName Grogan
313 schema:givenName Tristan R.
314 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0713510152.12
315 rdf:type schema:Person
316 sg:person.0737320651.15 schema:affiliation https://www.grid.ac/institutes/grid.421940.a
317 schema:familyName Emerson
318 schema:givenName Ryan O.
319 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0737320651.15
320 rdf:type schema:Person
321 sg:person.0751246211.79 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
322 schema:familyName Kivork
323 schema:givenName Christine
324 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0751246211.79
325 rdf:type schema:Person
326 sg:person.0773374227.51 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
327 schema:familyName Tumeh
328 schema:givenName Paul C.
329 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0773374227.51
330 rdf:type schema:Person
331 sg:pub.10.1038/ncomms3680 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029134323
332 https://doi.org/10.1038/ncomms3680
333 rdf:type schema:CreativeWork
334 sg:pub.10.1038/nm1517 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039360772
335 https://doi.org/10.1038/nm1517
336 rdf:type schema:CreativeWork
337 sg:pub.10.1038/nrc3239 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047946992
338 https://doi.org/10.1038/nrc3239
339 rdf:type schema:CreativeWork
340 https://doi.org/10.1016/s0140-6736(14)60958-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012632588
341 rdf:type schema:CreativeWork
342 https://doi.org/10.1056/nejmoa020177 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017266513
343 rdf:type schema:CreativeWork
344 https://doi.org/10.1056/nejmoa051424 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029918763
345 rdf:type schema:CreativeWork
346 https://doi.org/10.1056/nejmoa1200690 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042896583
347 rdf:type schema:CreativeWork
348 https://doi.org/10.1056/nejmoa1200694 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047413837
349 rdf:type schema:CreativeWork
350 https://doi.org/10.1056/nejmoa1302369 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024659470
351 rdf:type schema:CreativeWork
352 https://doi.org/10.1056/nejmoa1305133 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042841008
353 rdf:type schema:CreativeWork
354 https://doi.org/10.1126/science.1129139 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021857158
355 rdf:type schema:CreativeWork
356 https://doi.org/10.1126/scitranslmed.3006504 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027702744
357 rdf:type schema:CreativeWork
358 https://doi.org/10.1158/0008-5472.can-13-2752 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015640008
359 rdf:type schema:CreativeWork
360 https://doi.org/10.1158/1078-0432.ccr-09-1624 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028571226
361 rdf:type schema:CreativeWork
362 https://doi.org/10.1158/1078-0432.ccr-13-2797 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018432563
363 rdf:type schema:CreativeWork
364 https://doi.org/10.1158/1078-0432.ccr-13-3271 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004953031
365 rdf:type schema:CreativeWork
366 https://doi.org/10.1158/2159-8290.cd-13-0458 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028088139
367 rdf:type schema:CreativeWork
368 https://doi.org/10.1182/blood-2009-04-217604 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014830407
369 rdf:type schema:CreativeWork
370 https://doi.org/10.1200/jco.2013.49.4757 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045388928
371 rdf:type schema:CreativeWork
372 https://doi.org/10.1200/jco.2013.53.0105 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047895673
373 rdf:type schema:CreativeWork
374 https://doi.org/10.1200/jco.2014.32.18_suppl.lba9000 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083398367
375 rdf:type schema:CreativeWork
376 https://www.grid.ac/institutes/grid.14925.3b schema:alternateName Institut Gustave Roussy
377 schema:name Gustave Roussy and INSERM U981, Villejuif, Paris Sud, France
378 rdf:type schema:Organization
379 https://www.grid.ac/institutes/grid.19006.3e schema:alternateName University of California Los Angeles
380 schema:name Jonsson Comprehensive Cancer Center, Los Angeles, California 90095, USA
381 University of California Los Angeles (UCLA), Los Angeles, California 90095, USA
382 rdf:type schema:Organization
383 https://www.grid.ac/institutes/grid.270240.3 schema:alternateName Fred Hutchinson Cancer Research Center
384 schema:name Adaptive Biotechnologies, Seattle, Washington 98102, USA
385 Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
386 rdf:type schema:Organization
387 https://www.grid.ac/institutes/grid.417993.1 schema:alternateName MSD (United States)
388 schema:name Merck & Co, Palo Alto, California 94304, USA
389 rdf:type schema:Organization
390 https://www.grid.ac/institutes/grid.421940.a schema:alternateName Adaptive Biotechnologies (United States)
391 schema:name Adaptive Biotechnologies, Seattle, Washington 98102, USA
392 rdf:type schema:Organization
 




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


...