Evidence map›Paper›PMID 37327114›Full record

ArticleBlood advances2023

Allelic variation of KIR and HLA tunes the cytolytic payload and determines functional hierarchy of NK cell repertoires.

Camille Philippon, Sudan Tao, Dennis Clement, Alvaro Haroun-Izquierdo, Katherine M Kichula, Herman Netskar, Ludwig Brandt, Vincent Sheng Oei, Minoru Kanaya, Pilar Maria Lanuza and 11 more

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Sensitization in Transplantation Assessment of Risk 2025 innate working group: The potential role of innate allorecognition in kidney allograft damage.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025
    Review
  2. Natural Killer Cell Education in Women With Recurrent Pregnancy Loss.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025
    Article
  3. Article
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 8 institutions in 4 countries.

Camille PhilipponPrecision Immunotherapy Alliance (PRIMA), Institute for Clinical medicine, The University of Oslo, Oslo, Norway.
Sudan TaoDepartment of Biomedical Informatics, and Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.
Dennis ClementPrecision Immunotherapy Alliance (PRIMA), Institute for Clinical medicine, The University of Oslo, Oslo, Norway.
Alvaro Haroun-IzquierdoDepartment of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-4557-3606
Katherine M KichulaDepartment of Biomedical Informatics, and Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.ORCID 0000-0002-9817-3043
Herman NetskarPrecision Immunotherapy Alliance (PRIMA), Institute for Clinical medicine, The University of Oslo, Oslo, Norway.ORCID 0000-0002-3081-9581
Ludwig BrandtDepartment of Applied Physics, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.ORCID 0000-0003-2040-3176
Vincent Sheng OeiPrecision Immunotherapy Alliance (PRIMA), Institute for Clinical medicine, The University of Oslo, Oslo, Norway.ORCID 0000-0002-9336-529X
Minoru KanayaPrecision Immunotherapy Alliance (PRIMA), Institute for Clinical medicine, The University of Oslo, Oslo, Norway.ORCID 0000-0002-0035-8657
Pilar Maria LanuzaDepartment of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
Marie SchafferDepartment of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
Jodie P GoodridgeFate Therapeutics Inc, San Diego, CA.ORCID 0000-0001-7531-6032
Amir HorowitzDepartment of Oncological Sciences, The Marc and Jennifer Lipshultz Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Faming ZhuBlood Center of Zhejiang Province, Key Laboratory of Blood Safety Research of Zhejiang Province, Hangzhou, Zhejiang, China.ORCID 0000-0002-1963-9176
Quirin HammerDepartment of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-2968-6061
Ebba SohlbergDepartment of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
Rakesh Kumar MajhiPrecision Immunotherapy Alliance (PRIMA), Institute for Clinical medicine, The University of Oslo, Oslo, Norway.
Lise KvebergPrecision Immunotherapy Alliance (PRIMA), Institute for Clinical medicine, The University of Oslo, Oslo, Norway.ORCID 0000-0001-9308-0641
Björn ÖnfeltDepartment of Applied Physics, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
Paul J NormanDepartment of Biomedical Informatics, and Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.
Karl-Johan MalmbergPrecision Immunotherapy Alliance (PRIMA), Institute for Clinical medicine, The University of Oslo, Oslo, Norway.ORCID 0000-0002-8718-9373
University of Oslo · NOKarolinska Institutet · SEBlood Center of Zhejiang Province · CNOslo University Hospital · NOScience for Life Laboratory · SEUniversity of Colorado Denver · USFate Therapeutics (United States) · USIcahn School of Medicine at Mount Sinai · US

Funding

Therapeutic Potential of Adaptive NK Cells in Cancer and TransplantationP01CA111412 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI FELICES, MARTIN · 2005 to 2025
$38.2M
University of Colorado Anschutz Medical Campus DRCP30DK116073 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LORI SUSSEL · 2020 to 2026
$10.8M
Evolution and Function of Immunogenetic Diversity across the Eastern HemisphereR01AI151549 · NIAID · UNIVERSITY OF COLORADO DENVER · PI Paul John Norman · 2022 to 2026
$3.9M
Natural Killer cells and the Immunogenetics of COVID-19R01AI158410 · NIAID · UNIVERSITY OF COLORADO DENVER · PI NORMAN, PAUL JOHN · 2021 to 2024
$2.9M
NCI NIH HHS P01 CA111412NIAID NIH HHS R01 AI151549NIAID NIH HHS R01 AI158410NIDDK NIH HHS P30 DK116073
6 · The paper itself

Abstract

The functionality of natural killer (NK) cells is tuned during education and is associated with remodeling of the lysosomal compartment. We hypothesized that genetic variation in killer cell immunoglobulin-like receptor (KIR) and HLA, which is known to influence the functional strength of NK cells, fine-tunes the payload of effector molecules stored in secretory lysosomes. To address this possibility, we performed a high-resolution analysis of KIR and HLA class I genes in 365 blood donors and linked genotypes to granzyme B loading and functional phenotypes. We found that granzyme B levels varied across individuals but were stable over time in each individual and genetically determined by allelic variation in HLA class I genes. A broad mapping of surface receptors and lysosomal effector molecules revealed that DNAM-1 and granzyme B levels served as robust metric of the functional state in NK cells. Variation in granzyme B levels at rest was tightly linked to the lytic hit and downstream killing of major histocompatibility complex-deficient target cells. Together, these data provide insights into how variation in genetically hardwired receptor pairs tunes the releasable granzyme B pool in NK cells, resulting in predictable hierarchies in global NK cell function.

Indexed as

Killer Cells, NaturalReceptors, KIRGenotypeGranzymesHistocompatibility Antigens Class IGranzymesHistocompatibility Antigens Class IReceptors, KIR

Identifiers

PMID37327114
PMCPMC10440473
OpenAlexW4380985670

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.