Evidence map›Paper›PMID 40838628›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2025

The transcription factor BCL11B drives NK cell cytotoxicity and antitumor activity.

Akhilesh Kumar, Bin Zhang, Andrew Baldys, Colin Fischer, Alexander Lenvik, Martin Felices, Zachary B Davis, Laura Bendzick, Anna J Weis, Yenan T Bryceson and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

12 authors.

Akhilesh KumarDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Bin ZhangDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Andrew BaldysDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Colin FischerDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Alexander LenvikDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Martin FelicesDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Zachary B DavisDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Laura BendzickDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Anna J WeisDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.ORCID 0009-0003-9158-3634
Yenan T BrycesonBroegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway.
Jeffrey S MillerDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Frank CichockiDepartment of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
Therapeutic Potential of Adaptive NK Cells in Cancer and TransplantationP01CA111412 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MILLER, JEFFREY S. · 2005 to 2025
$38.2M
Viral priming and targeting NK cells against solid tumor malignanciesR35CA197292 · NCI · UNIVERSITY OF MINNESOTA · PI MILLER, JEFFREY S. · 2015 to 2021
$6.2M
Bcl11b: A Master Transcription Factor Controlling Human NK Cell DevelopmentR01HL155150 · NHLBI · UNIVERSITY OF MINNESOTA · PI CICHOCKI, FRANK · 2021 to 2025
$1.6M
Cichocki and National Cancer Institute, National Institutes of Health Grants P01 CA65493NCI NIH HHS P01 CA065493NCI NIH HHS P01 CA111412NCI NIH HHS R35 CA197292NHLBI NIH HHS R01 HL155150NIH HHS P01 CA111412NIH HHS P01 CA65493NIH HHS R01 HL155150NIH HHS R35 CA197292
6 · The paper itself

Abstract

Bcl11b is a zinc-finger transcription factor that is required for the differentiation of αβ T cells. A role for BCL11B in the regulation of human natural killer (NK) cell maturation has been inferred from patients with heterozygous mutations in BCL11B. However, mechanistic and functional studies are lacking due to the low efficiency of current transduction and transfection methods. Here, we developed a synthetic BCL11B mRNA with enhanced stability that could be transfected into primary NK cells at high frequencies. Introduction of BCL11B mRNA slowed NK cell proliferation while simultaneously driving maturation and acquisition of cytotoxic granule components. For in vitro and in vivo functional testing, we generated induced pluripotent stem cell (iPSC)-derived NK (iNK) cells with inducible BCL11B expression. These iNK cells mediated faster solid tumor cell killing and significantly better tumor control in vivo. Together, our findings support the notion that BCL11B is a key transcription factor in human NK cells and demonstrate that increased BCL11B expression can enhance NK cell immunotherapy.

Indexed as

Cytotoxicity, ImmunologicKiller Cells, NaturalRepressor ProteinsTumor Suppressor ProteinsAnimalsCell Line, TumorHumansInduced Pluripotent Stem CellsMiceRNA, MessengerBCL11B protein, humanRepressor ProteinsRNA, MessengerTumor Suppressor Proteinsmaturationnatural killertranscription factor

Identifiers

PMID40838628
PMCPMC12646058

What OpenQuestion holds

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Registered trials

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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.