HHLA2 in intrahepatic cholangiocarcinoma: an immune checkpoint with prognostic significance and wider expression compared with PD-L1 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Chu-Yu Jing, Yi-Peng Fu, Yong Yi, Mei-Xia Zhang, Su-Su Zheng, Jin-Long Huang, Wei Gan, Xin Xu, Jia-Jia Lin, Juan Zhang, Shuang-Jian Qiu, Bo-Heng Zhang

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly mortal malignancy with limited therapeutic options. Immunotherapies targeting PD-1/PD-L1 pathway represent a promising treatment for ICC. However, PD-L1 expression and microsatellite instability are not common in ICC. This study aimed to investigate whether HHLA2, a newly identified B7 family immune checkpoint for T cells, could be a therapeutic target next to PD-L1 in ICC. METHODS: Expression levels of PD-L1 and HHLA2 as well as infiltrations of CD3+, CD8+, CD4 + Foxp3+, CD68+, CD163+ and CD20+ cells were evaluated by immunohistochemistry in 153 resected ICC samples. Comprehensive comparisons were made between PD-L1 and HHLA2 in terms of the expression rates, clinicopathological features and infiltrations of different immune cells. The expression level and prognostic significance of HHLA2 were further validated in an independent cohort. RESULTS: Expression of HHLA2 is more frequent than PD-L1 in ICC (49.0% vs 28.1%). Co-expression of both immune checkpoints was infrequent (13.1%) and 50% PD-L1 negative cases were with elevated HHLA2. HHLA2 overexpression was associated with sparser CD3+ tumor infiltrating lymphocytes (TILs), CD8+ TILs and a higher CD4 + Foxp3+/CD8+ TIL ratio, whereas PD-L1 expression was associated with prominent T cells and CD163+ tumor associated macrophages infiltrations. PD-L1 failed to stratify overall survival (OS) but HHLA2 was identified as an independent prognostic indicator for OS in two independent cohorts. CONCLUSIONS: Compared with PD-L1, HHLA2 is more prevalent and possesses more explicit prognostic significance, which confer the rationale for HHLA2 as a potential immunotherapeutic target next to PD-L1 for ICC patients. More... »

PAGES

77

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40425-019-0554-8

DOI

http://dx.doi.org/10.1186/s40425-019-0554-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112859036

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30885276


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"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "Fudan University Shanghai Cancer Center, 270 Dong-An Road, 200032, Shanghai, People\u2019s Republic of China", 
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Jing", 
        "givenName": "Chu-Yu", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Obstetrics and Gynecology Hospital of Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.412312.7", 
          "name": [
            "Department of breast surgery, The Obstetrics & Gynecology Hospital of Fudan University, 419 Fangxie Road, 200090, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Fu", 
        "givenName": "Yi-Peng", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yi", 
        "givenName": "Yong", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zhang", 
        "givenName": "Mei-Xia", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zheng", 
        "givenName": "Su-Su", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Huang", 
        "givenName": "Jin-Long", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gan", 
        "givenName": "Wei", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Xu", 
        "givenName": "Xin", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lin", 
        "givenName": "Jia-Jia", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zhang", 
        "givenName": "Juan", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Qiu", 
        "givenName": "Shuang-Jian", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People\u2019s Republic of China", 
            "Center for evidence-based medicine, Shanghai Medical School, Fudan University, 200032, Shanghai, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zhang", 
        "givenName": "Bo-Heng", 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1073/pnas.1303524110", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000938991"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2014.57.9151", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002455355"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1245/s10434-016-5101-y", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004744850", 
          "https://doi.org/10.1245/s10434-016-5101-y"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2012.41.5984", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007738909"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1634/theoncologist.2014-0470", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008381082"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-14-1495", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008432824"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-12-1362", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010896222"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2006.09.4565", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018563763"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep31154", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023588193", 
          "https://doi.org/10.1038/srep31154"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1091/mbc.e11-11-0934", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024624648"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.intimp.2016.01.023", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031886280"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jhep.2014.01.021", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040146502"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.14530", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043618036"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/sla.0b013e318176c4d3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045077536"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/sla.0b013e318176c4d3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045077536"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/bjc.2016.47", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045304836", 
          "https://doi.org/10.1038/bjc.2016.47"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-15-0715", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050825675"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ccell.2015.03.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053023000"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrclinonc.2015.209", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053702845", 
          "https://doi.org/10.1038/nrclinonc.2015.209"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-16-0150", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1054005133"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/2162402x.2015.1026534", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1058420489"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-15-3071", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063225295"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/2159-8290.cd-nb2017-079", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085767669"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jso.24720", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085991236"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/mcs.a001974", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1086128505"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2017.74.7642", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092312928"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-17-2924", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1100667028"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-17-2011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1101895685"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1634/theoncologist.2017-0439", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107227645"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2147/cmar.s172719", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107341330"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2018.09.035", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107392616"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa1809615", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107740741"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa1809615", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107740741"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41416-018-0199-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107912892", 
          "https://doi.org/10.1038/s41416-018-0199-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41416-018-0199-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107912892", 
          "https://doi.org/10.1038/s41416-018-0199-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41416-018-0199-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107912892", 
          "https://doi.org/10.1038/s41416-018-0199-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1136/gutjnl-2018-316324", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1111542474"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1136/gutjnl-2018-316324", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1111542474"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-18-3208", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1111641232"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-18-3208", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1111641232"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2019-12", 
    "datePublishedReg": "2019-12-01", 
    "description": "BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly mortal malignancy with limited therapeutic options. Immunotherapies targeting PD-1/PD-L1 pathway represent a promising treatment for ICC. However, PD-L1 expression and microsatellite instability are not common in ICC. This study aimed to investigate whether HHLA2, a newly identified B7 family immune checkpoint for T cells, could be a therapeutic target next to PD-L1 in ICC.\nMETHODS: Expression levels of PD-L1 and HHLA2 as well as infiltrations of CD3+, CD8+, CD4\u2009+\u2009Foxp3+, CD68+, CD163+ and CD20+ cells were evaluated by immunohistochemistry in 153 resected ICC samples. Comprehensive comparisons were made between PD-L1 and HHLA2 in terms of the expression rates, clinicopathological features and infiltrations of different immune cells. The expression level and prognostic significance of HHLA2 were further validated in an independent cohort.\nRESULTS: Expression of HHLA2 is more frequent than PD-L1 in ICC (49.0% vs 28.1%). Co-expression of both immune checkpoints was infrequent (13.1%) and 50% PD-L1 negative cases were with elevated HHLA2. HHLA2 overexpression was associated with sparser CD3+ tumor infiltrating lymphocytes (TILs), CD8+ TILs and a higher CD4\u2009+\u2009Foxp3+/CD8+ TIL ratio, whereas PD-L1 expression was associated with prominent T cells and CD163+ tumor associated macrophages infiltrations. PD-L1 failed to stratify overall survival (OS) but HHLA2 was identified as an independent prognostic indicator for OS in two independent cohorts.\nCONCLUSIONS: Compared with PD-L1, HHLA2 is more prevalent and possesses more explicit prognostic significance, which confer the rationale for HHLA2 as a potential immunotherapeutic target next to PD-L1 for ICC patients.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1186/s40425-019-0554-8", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1049249", 
        "issn": [
          "2051-1426"
        ], 
        "name": "Journal for ImmunoTherapy of Cancer", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "7"
      }
    ], 
    "name": "HHLA2 in intrahepatic cholangiocarcinoma: an immune checkpoint with prognostic significance and wider expression compared with PD-L1", 
    "pagination": "77", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "fe79b88905b439f6de76740d219cc81df9cec92aafbaab6b74920ecc795c6be6"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30885276"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101620585"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s40425-019-0554-8"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1112859036"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s40425-019-0554-8", 
      "https://app.dimensions.ai/details/publication/pub.1112859036"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T13:21", 
    "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/v90/0000000368_0000000368/records_78974_00000001.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1186%2Fs40425-019-0554-8"
  }
]
 

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.10.1186/s40425-019-0554-8'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s40425-019-0554-8'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s40425-019-0554-8'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s40425-019-0554-8'


 

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

245 TRIPLES      21 PREDICATES      63 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s40425-019-0554-8 schema:about anzsrc-for:11
2 anzsrc-for:1107
3 schema:author N0ce6302a9e39408fb37f583f66f9692c
4 schema:citation sg:pub.10.1038/bjc.2016.47
5 sg:pub.10.1038/nrclinonc.2015.209
6 sg:pub.10.1038/s41416-018-0199-2
7 sg:pub.10.1038/srep31154
8 sg:pub.10.1245/s10434-016-5101-y
9 https://doi.org/10.1002/jso.24720
10 https://doi.org/10.1016/j.ccell.2015.03.001
11 https://doi.org/10.1016/j.cell.2018.09.035
12 https://doi.org/10.1016/j.intimp.2016.01.023
13 https://doi.org/10.1016/j.jhep.2014.01.021
14 https://doi.org/10.1056/nejmoa1809615
15 https://doi.org/10.1073/pnas.1303524110
16 https://doi.org/10.1080/2162402x.2015.1026534
17 https://doi.org/10.1091/mbc.e11-11-0934
18 https://doi.org/10.1097/sla.0b013e318176c4d3
19 https://doi.org/10.1101/mcs.a001974
20 https://doi.org/10.1136/gutjnl-2018-316324
21 https://doi.org/10.1158/0008-5472.can-17-2011
22 https://doi.org/10.1158/0008-5472.can-18-3208
23 https://doi.org/10.1158/1078-0432.ccr-12-1362
24 https://doi.org/10.1158/1078-0432.ccr-14-1495
25 https://doi.org/10.1158/1078-0432.ccr-15-0715
26 https://doi.org/10.1158/1078-0432.ccr-15-3071
27 https://doi.org/10.1158/1078-0432.ccr-16-0150
28 https://doi.org/10.1158/1078-0432.ccr-17-2924
29 https://doi.org/10.1158/2159-8290.cd-nb2017-079
30 https://doi.org/10.1200/jco.2006.09.4565
31 https://doi.org/10.1200/jco.2012.41.5984
32 https://doi.org/10.1200/jco.2014.57.9151
33 https://doi.org/10.1200/jco.2017.74.7642
34 https://doi.org/10.1634/theoncologist.2014-0470
35 https://doi.org/10.1634/theoncologist.2017-0439
36 https://doi.org/10.18632/oncotarget.14530
37 https://doi.org/10.2147/cmar.s172719
38 schema:datePublished 2019-12
39 schema:datePublishedReg 2019-12-01
40 schema:description BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly mortal malignancy with limited therapeutic options. Immunotherapies targeting PD-1/PD-L1 pathway represent a promising treatment for ICC. However, PD-L1 expression and microsatellite instability are not common in ICC. This study aimed to investigate whether HHLA2, a newly identified B7 family immune checkpoint for T cells, could be a therapeutic target next to PD-L1 in ICC. METHODS: Expression levels of PD-L1 and HHLA2 as well as infiltrations of CD3+, CD8+, CD4 + Foxp3+, CD68+, CD163+ and CD20+ cells were evaluated by immunohistochemistry in 153 resected ICC samples. Comprehensive comparisons were made between PD-L1 and HHLA2 in terms of the expression rates, clinicopathological features and infiltrations of different immune cells. The expression level and prognostic significance of HHLA2 were further validated in an independent cohort. RESULTS: Expression of HHLA2 is more frequent than PD-L1 in ICC (49.0% vs 28.1%). Co-expression of both immune checkpoints was infrequent (13.1%) and 50% PD-L1 negative cases were with elevated HHLA2. HHLA2 overexpression was associated with sparser CD3+ tumor infiltrating lymphocytes (TILs), CD8+ TILs and a higher CD4 + Foxp3+/CD8+ TIL ratio, whereas PD-L1 expression was associated with prominent T cells and CD163+ tumor associated macrophages infiltrations. PD-L1 failed to stratify overall survival (OS) but HHLA2 was identified as an independent prognostic indicator for OS in two independent cohorts. CONCLUSIONS: Compared with PD-L1, HHLA2 is more prevalent and possesses more explicit prognostic significance, which confer the rationale for HHLA2 as a potential immunotherapeutic target next to PD-L1 for ICC patients.
41 schema:genre research_article
42 schema:inLanguage en
43 schema:isAccessibleForFree true
44 schema:isPartOf N4778775f0e454de8b05cf93ee467566d
45 N775f93431df743d6b9bcd02dea4762be
46 sg:journal.1049249
47 schema:name HHLA2 in intrahepatic cholangiocarcinoma: an immune checkpoint with prognostic significance and wider expression compared with PD-L1
48 schema:pagination 77
49 schema:productId N8e01dd2a6fe341ed943515a9f0b3c531
50 Nac4217900cea44aaa4e604adad501e64
51 Naf13bbb4334e400bae39e910597c0601
52 Nec6a0b5ee6f143a4bf95535a6ddf29d7
53 Nedad0cdce579462ab5b1b9d3d7c7c19c
54 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112859036
55 https://doi.org/10.1186/s40425-019-0554-8
56 schema:sdDatePublished 2019-04-11T13:21
57 schema:sdLicense https://scigraph.springernature.com/explorer/license/
58 schema:sdPublisher N24f02b9cd29a4063bd74e21f03ac58cc
59 schema:url https://link.springer.com/10.1186%2Fs40425-019-0554-8
60 sgo:license sg:explorer/license/
61 sgo:sdDataset articles
62 rdf:type schema:ScholarlyArticle
63 N026911e4cda7450c856bbe67a41bfe07 schema:affiliation https://www.grid.ac/institutes/grid.8547.e
64 schema:familyName Jing
65 schema:givenName Chu-Yu
66 rdf:type schema:Person
67 N0b61041f1bd449b5906c32e84aac9e63 schema:affiliation https://www.grid.ac/institutes/grid.412312.7
68 schema:familyName Fu
69 schema:givenName Yi-Peng
70 rdf:type schema:Person
71 N0cb9cc513d2540198434b1f34f49ea0a rdf:first Nb377de4a34ec4df6b9ecc6bda1b094e1
72 rdf:rest N5e9e13e285a9428f99823b3da12610e6
73 N0ce6302a9e39408fb37f583f66f9692c rdf:first N026911e4cda7450c856bbe67a41bfe07
74 rdf:rest Nc5239174e7a947d4a02b800c296e9eda
75 N0ce6b4893c104dcdb8c956f3b1c2341b rdf:first N68c48682acb74716b442ba0d6c42245a
76 rdf:rest Nfdbe308e44954e7082fba7a4be1c47d0
77 N24f02b9cd29a4063bd74e21f03ac58cc schema:name Springer Nature - SN SciGraph project
78 rdf:type schema:Organization
79 N2f533d6018f04226a3ae86334c7db0ce schema:affiliation https://www.grid.ac/institutes/grid.8547.e
80 schema:familyName Xu
81 schema:givenName Xin
82 rdf:type schema:Person
83 N38d71e7e00d841fe8e7d44a65c2e6732 rdf:first N898600d5e15045a6805610fa8cd3d9a8
84 rdf:rest N4df78b6f597a42fd8b82b9f1f8f466bd
85 N3b3dc8f7e40e4dd38abacf26384a0f7a schema:affiliation https://www.grid.ac/institutes/grid.8547.e
86 schema:familyName Zheng
87 schema:givenName Su-Su
88 rdf:type schema:Person
89 N3ced764970a74f39a8945959f1eb9ca8 rdf:first Nd0d5092fe853426698a9d15d2a27c29e
90 rdf:rest N0cb9cc513d2540198434b1f34f49ea0a
91 N4258a20398664842814b8aab6118824f rdf:first N99602f9676eb4cc28f483feff78cff2f
92 rdf:rest Nb668858f77cc41b988bb994e11fd31e2
93 N4778775f0e454de8b05cf93ee467566d schema:volumeNumber 7
94 rdf:type schema:PublicationVolume
95 N4df78b6f597a42fd8b82b9f1f8f466bd rdf:first Ndc9137865ab14febb8d571fd46112011
96 rdf:rest N4258a20398664842814b8aab6118824f
97 N5e9e13e285a9428f99823b3da12610e6 rdf:first N3b3dc8f7e40e4dd38abacf26384a0f7a
98 rdf:rest N0ce6b4893c104dcdb8c956f3b1c2341b
99 N68c48682acb74716b442ba0d6c42245a schema:affiliation https://www.grid.ac/institutes/grid.8547.e
100 schema:familyName Huang
101 schema:givenName Jin-Long
102 rdf:type schema:Person
103 N775f93431df743d6b9bcd02dea4762be schema:issueNumber 1
104 rdf:type schema:PublicationIssue
105 N898600d5e15045a6805610fa8cd3d9a8 schema:affiliation https://www.grid.ac/institutes/grid.8547.e
106 schema:familyName Lin
107 schema:givenName Jia-Jia
108 rdf:type schema:Person
109 N8e01dd2a6fe341ed943515a9f0b3c531 schema:name readcube_id
110 schema:value fe79b88905b439f6de76740d219cc81df9cec92aafbaab6b74920ecc795c6be6
111 rdf:type schema:PropertyValue
112 N92c56729961d4554ae7b8ee82e0ba477 rdf:first N2f533d6018f04226a3ae86334c7db0ce
113 rdf:rest N38d71e7e00d841fe8e7d44a65c2e6732
114 N99602f9676eb4cc28f483feff78cff2f schema:affiliation https://www.grid.ac/institutes/grid.8547.e
115 schema:familyName Qiu
116 schema:givenName Shuang-Jian
117 rdf:type schema:Person
118 N9f609c8fdb974691907530e5619730fc schema:affiliation https://www.grid.ac/institutes/grid.8547.e
119 schema:familyName Zhang
120 schema:givenName Bo-Heng
121 rdf:type schema:Person
122 Nac4217900cea44aaa4e604adad501e64 schema:name dimensions_id
123 schema:value pub.1112859036
124 rdf:type schema:PropertyValue
125 Naf13bbb4334e400bae39e910597c0601 schema:name pubmed_id
126 schema:value 30885276
127 rdf:type schema:PropertyValue
128 Nb377de4a34ec4df6b9ecc6bda1b094e1 schema:affiliation https://www.grid.ac/institutes/grid.8547.e
129 schema:familyName Zhang
130 schema:givenName Mei-Xia
131 rdf:type schema:Person
132 Nb668858f77cc41b988bb994e11fd31e2 rdf:first N9f609c8fdb974691907530e5619730fc
133 rdf:rest rdf:nil
134 Nc5239174e7a947d4a02b800c296e9eda rdf:first N0b61041f1bd449b5906c32e84aac9e63
135 rdf:rest N3ced764970a74f39a8945959f1eb9ca8
136 Nd0d5092fe853426698a9d15d2a27c29e schema:affiliation https://www.grid.ac/institutes/grid.8547.e
137 schema:familyName Yi
138 schema:givenName Yong
139 rdf:type schema:Person
140 Ndc9137865ab14febb8d571fd46112011 schema:affiliation https://www.grid.ac/institutes/grid.8547.e
141 schema:familyName Zhang
142 schema:givenName Juan
143 rdf:type schema:Person
144 Nec6a0b5ee6f143a4bf95535a6ddf29d7 schema:name doi
145 schema:value 10.1186/s40425-019-0554-8
146 rdf:type schema:PropertyValue
147 Nedad0cdce579462ab5b1b9d3d7c7c19c schema:name nlm_unique_id
148 schema:value 101620585
149 rdf:type schema:PropertyValue
150 Nfdbe308e44954e7082fba7a4be1c47d0 rdf:first Nfe816274afe34abba8116506ab8e274f
151 rdf:rest N92c56729961d4554ae7b8ee82e0ba477
152 Nfe816274afe34abba8116506ab8e274f schema:affiliation https://www.grid.ac/institutes/grid.8547.e
153 schema:familyName Gan
154 schema:givenName Wei
155 rdf:type schema:Person
156 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
157 schema:name Medical and Health Sciences
158 rdf:type schema:DefinedTerm
159 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
160 schema:name Immunology
161 rdf:type schema:DefinedTerm
162 sg:journal.1049249 schema:issn 2051-1426
163 schema:name Journal for ImmunoTherapy of Cancer
164 rdf:type schema:Periodical
165 sg:pub.10.1038/bjc.2016.47 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045304836
166 https://doi.org/10.1038/bjc.2016.47
167 rdf:type schema:CreativeWork
168 sg:pub.10.1038/nrclinonc.2015.209 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053702845
169 https://doi.org/10.1038/nrclinonc.2015.209
170 rdf:type schema:CreativeWork
171 sg:pub.10.1038/s41416-018-0199-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107912892
172 https://doi.org/10.1038/s41416-018-0199-2
173 rdf:type schema:CreativeWork
174 sg:pub.10.1038/srep31154 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023588193
175 https://doi.org/10.1038/srep31154
176 rdf:type schema:CreativeWork
177 sg:pub.10.1245/s10434-016-5101-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1004744850
178 https://doi.org/10.1245/s10434-016-5101-y
179 rdf:type schema:CreativeWork
180 https://doi.org/10.1002/jso.24720 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085991236
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1016/j.ccell.2015.03.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053023000
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1016/j.cell.2018.09.035 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107392616
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1016/j.intimp.2016.01.023 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031886280
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1016/j.jhep.2014.01.021 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040146502
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1056/nejmoa1809615 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107740741
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1073/pnas.1303524110 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000938991
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1080/2162402x.2015.1026534 schema:sameAs https://app.dimensions.ai/details/publication/pub.1058420489
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1091/mbc.e11-11-0934 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024624648
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1097/sla.0b013e318176c4d3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045077536
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1101/mcs.a001974 schema:sameAs https://app.dimensions.ai/details/publication/pub.1086128505
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1136/gutjnl-2018-316324 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111542474
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1158/0008-5472.can-17-2011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101895685
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1158/0008-5472.can-18-3208 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111641232
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1158/1078-0432.ccr-12-1362 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010896222
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1158/1078-0432.ccr-14-1495 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008432824
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1158/1078-0432.ccr-15-0715 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050825675
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1158/1078-0432.ccr-15-3071 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063225295
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1158/1078-0432.ccr-16-0150 schema:sameAs https://app.dimensions.ai/details/publication/pub.1054005133
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1158/1078-0432.ccr-17-2924 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100667028
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1158/2159-8290.cd-nb2017-079 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085767669
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1200/jco.2006.09.4565 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018563763
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1200/jco.2012.41.5984 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007738909
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1200/jco.2014.57.9151 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002455355
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1200/jco.2017.74.7642 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092312928
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1634/theoncologist.2014-0470 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008381082
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1634/theoncologist.2017-0439 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107227645
233 rdf:type schema:CreativeWork
234 https://doi.org/10.18632/oncotarget.14530 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043618036
235 rdf:type schema:CreativeWork
236 https://doi.org/10.2147/cmar.s172719 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107341330
237 rdf:type schema:CreativeWork
238 https://www.grid.ac/institutes/grid.412312.7 schema:alternateName Obstetrics and Gynecology Hospital of Fudan University
239 schema:name Department of breast surgery, The Obstetrics & Gynecology Hospital of Fudan University, 419 Fangxie Road, 200090, Shanghai, People’s Republic of China
240 rdf:type schema:Organization
241 https://www.grid.ac/institutes/grid.8547.e schema:alternateName Fudan University
242 schema:name Center for evidence-based medicine, Shanghai Medical School, Fudan University, 200032, Shanghai, People’s Republic of China
243 Fudan University Shanghai Cancer Center, 270 Dong-An Road, 200032, Shanghai, People’s Republic of China
244 The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, 200032, Shanghai, People’s Republic of China
245 rdf:type schema:Organization
 




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


...