Evidence map›Paper›PMID 29942093›Full record

ArticleNature medicine2018

A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments.

Kevin C Barry, Joy Hsu, Miranda L Broz, Francisco J Cueto, Mikhail Binnewies, Alexis J Combes, Amanda E Nelson, Kimberly Loo, Raj Kumar, Michael D Rosenblum and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 646 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
646citing papers in PubMed, 2 pooled it
39.7field-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

646 citing papers in PubMed, 2 syntheses or guidelines pooled it, 984 citations in OpenAlex.

  1. Pooled it
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  17. Tumor-Infiltrating mregDCs Restrain Anti-Tumor Immunity in Early Relapse HCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  18. Review
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586 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 2 institutions in 2 countries.

Kevin C BarryDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1064-5964
Joy HsuDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Miranda L BrozDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Francisco J CuetoDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Mikhail BinnewiesDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Alexis J CombesDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Amanda E NelsonDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Kimberly LooUCSF Immunoprofiler Initiative, University of California San Francisco, San Francisco, CA, USA.
Raj KumarDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Michael D RosenblumDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Michael D AlvaradoDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.
Denise M WolfDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Dusan BogunovicDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nina BhardwajTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Adil I DaudDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6617-8421
Patrick K HaDepartment of Otolaryngology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0306-6147
William R RyanDepartment of Otolaryngology, University of California San Francisco, San Francisco, CA, USA.
Joshua L PollackPionyr Immunotherapeutics, San Francisco, CA, USA.
Bushra SamadDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Saurabh AsthanaUCSF Immunoprofiler Initiative, University of California San Francisco, San Francisco, CA, USA.
Vincent ChanDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Matthew F KrummelDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA. matthew.krummel@ucsf.edu.ORCID http://orcid.org/0000-0001-7915-3533
University of California, San Francisco · USIcahn School of Medicine at Mount Sinai · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kate Taylor Shumate · 1999 to 2026
$209.7M
MOLECULAR AND CELLULAR IMMUNOLOGYT32AI007334 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CYSTER, JASON G · 1988 to 2023
$11.0M
PREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7M
The Tumor Microenvironment Niche of Type I conventional Dendritic CellsR01CA197363 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MATTHEW F KRUMMEL · 2017 to 2026
$4.5M
Functional Manipulation of Memory Regulatory T cells in SkinDP2AR068130 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSENBLUM, MICHAEL DAVID · 2014 to 2014
$2.4M
Manipulating collectivity and Niches for Developing CD8 ImmunityR01AI114787 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2015 to 2019
$2.2M
NCI NIH HHS P30 CA082103NCI NIH HHS R01 CA197363NIAID NIH HHS R01 AI114787NIAID NIH HHS T32 AI007334NIAMS NIH HHS DP2 AR068130NICHD NIH HHS T32 HD007470
6 · The paper itself

Abstract

Intratumoral stimulatory dendritic cells (SDCs) play an important role in stimulating cytotoxic T cells and driving immune responses against cancer. Understanding the mechanisms that regulate their abundance in the tumor microenvironment (TME) could unveil new therapeutic opportunities. We find that in human melanoma, SDC abundance is associated with intratumoral expression of the gene encoding the cytokine FLT3LG. FLT3LG is predominantly produced by lymphocytes, notably natural killer (NK) cells in mouse and human tumors. NK cells stably form conjugates with SDCs in the mouse TME, and genetic and cellular ablation of NK cells in mice demonstrates their importance in positively regulating SDC abundance in tumor through production of FLT3L. Although anti-PD-1 'checkpoint' immunotherapy for cancer largely targets T cells, we find that NK cell frequency correlates with protective SDCs in human cancers, with patient responsiveness to anti-PD-1 immunotherapy, and with increased overall survival. Our studies reveal that innate immune SDCs and NK cells cluster together as an excellent prognostic tool for T cell-directed immunotherapy and that these innate cells are necessary for enhanced T cell tumor responses, suggesting this axis as a target for new therapies.

Indexed as

ImmunotherapyAntigens, SurfaceCell CommunicationCell SurvivalDendritic CellsHumansKiller Cells, NaturalLymphocytesMelanomaMembrane ProteinsSurvival AnalysisThrombomodulinTumor MicroenvironmentAntigens, Surfaceflt3 ligand proteinMembrane ProteinsTHBD protein, humanThrombomodulin

Identifiers

PMID29942093
PMCPMC6475503
OpenAlexW2808909747

What OpenQuestion holds

Textmetadata
LicenceTDM
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.