Evidence map›Paper›PMID 30198904›Full record

ArticleThe Journal of clinical investigation2018

Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade.

Joy Hsu, Jonathan J Hodgins, Malvika Marathe, Chris J Nicolai, Marie-Claude Bourgeois-Daigneault, Troy N Trevino, Camillia S Azimi, Amit K Scheer, Haley E Randolph, Thornton W Thompson and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 565 papers.

0numbers the graph read from it
0cells of the map it votes in
565citing papers in PubMed
33.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

565 citing papers in PubMed, 807 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Trial
  4. Trial
  5. Molecular imaging usingAnnals of nuclear medicine · 2025
    Trial
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Article
  11. Article
  12. Therapeutic bacteria-trained NK cells confer long-term protection against cancer metastasis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Umbilical cord blood-derived natural killer cells:Annals of medicine and surgery (2012) · 2026
    Article
  19. Review
  20. Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026
    Review

505 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 2 institutions in 2 countries.

Joy HsuDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
Jonathan J HodginsDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Malvika MaratheDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
Chris J NicolaiDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
Marie-Claude Bourgeois-DaigneaultDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Troy N TrevinoDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
Camillia S AzimiDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
Amit K ScheerDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Haley E RandolphDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
Thornton W ThompsonDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
Lily ZhangDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
Alexandre IannelloDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
Nikhita MathurDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Karen E JardineDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Georgia A KirnDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
John C BellDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Michael W McBurneyDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
David H RauletDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
Michele ArdolinoDepartment of Molecular and Cell Biology, Immunotherapy and Vaccine Research Initiative, Cancer Research Laboratory, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, USA.
University of California, Berkeley · USUniversity of Ottawa · CA

Funding

THE MOLECULAR BASIS OF CELL FUNCTIONT32GM007232 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI BILDER, DAVID, UNAL, ELCIN · 1985 to 2022
$36.4M
Role of NKG2D in immune responses to turmorsR01CA093678 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI RAULET, DAVID H · 2003 to 2019
$4.2M
STING-dependent activation of Natural Killer cells by viral and tumor DNAR01AI113041 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI RAULET, DAVID H · 2014 to 2024
$4.1M
CIHRNCI NIH HHS R01 CA093678NIAID NIH HHS R01 AI113041NIGMS NIH HHS T32 GM007232
6 · The paper itself

Abstract

Checkpoint blockade immunotherapy targeting the PD-1/PD-L1 inhibitory axis has produced remarkable results in the treatment of several types of cancer. Whereas cytotoxic T cells are known to provide important antitumor effects during checkpoint blockade, certain cancers with low MHC expression are responsive to therapy, suggesting that other immune cell types may also play a role. Here, we employed several mouse models of cancer to investigate the effect of PD-1/PD-L1 blockade on NK cells, a population of cytotoxic innate lymphocytes that also mediate antitumor immunity. We discovered that PD-1 and PD-L1 blockade elicited a strong NK cell response that was indispensable for the full therapeutic effect of immunotherapy. PD-1 was expressed on NK cells within transplantable, spontaneous, and genetically induced mouse tumor models, and PD-L1 expression in cancer cells resulted in reduced NK cell responses and generation of more aggressive tumors in vivo. PD-1 expression was more abundant on NK cells with an activated and more responsive phenotype and did not mark NK cells with an exhausted phenotype. These results demonstrate the importance of the PD-1/PD-L1 axis in inhibiting NK cell responses in vivo and reveal that NK cells, in addition to T cells, mediate the effect of PD-1/PD-L1 blockade immunotherapy.

Indexed as

ImmunotherapyAnimalsB7-H1 AntigenHumansK562 CellsKiller Cells, NaturalMiceMice, KnockoutNeoplasms, ExperimentalProgrammed Cell Death 1 ReceptorB7-H1 AntigenCd274 protein, mousePdcd1 protein, mouseProgrammed Cell Death 1 ReceptorImmunologyImmunotherapyInnate immunityNK cells

Identifiers

PMID30198904
PMCPMC6159991
OpenAlexW2890056446

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.