Evidence map›Paper›PMID 41023081›Full record

ArticleScientific reports2025

Selective agonists of KIR and NKG2A to evade missing self response of natural killer cells.

Satoshi Hiura, Yuto Kuwasaki, Yosuke Nishikawa, Takako Kimura, Sayaka Yoshida, Makiko Nakayama, Tomohiro Makino, Suguru Ueno

Abstract read
In one paragraph

Article in Scientific reports, 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

8 authors.

Satoshi Hiura *Discovery Research Laboratories V, Daiichi Sankyo Co., Ltd., Tokyo, Japan. satoshi.hiura@daiichisankyo.com.
Yuto Kuwasaki *Discovery Research Laboratories V, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Yosuke NishikawaModality Research Laboratories I, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Takako KimuraModality Research Laboratories I, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Sayaka YoshidaDiscovery Research Laboratories V, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Makiko NakayamaModality Research Laboratories II, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Tomohiro MakinoBioprocess Technology Research Laboratories I, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Suguru UenoBioprocess Technology Research Laboratories II, Daiichi Sankyo Co., Ltd., Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immune rejection is one of the most serious challenges in allogeneic transplantation, including allogeneic induced pluripotent stem cell (allo-iPSC)-derived cell therapy. Beta-2-Microglobulin gene-knockout, human leukocyte antigen (HLA) class I-deficient iPSCs can evade immune rejection by host T cells, which occurs due to HLA mismatches. However, natural killer (NK) cells recognize HLA class Ⅰ-deficient cells and reject them, which is known as the missing-self response. Introducing chimeric HLA-E protein to HLA class Ⅰ-deficient iPSCs suppresses the missing-self response of NK cells expressing the inhibitory receptor NKG2A; however, technology to suppress NKG2A-negative NK cells is still required. Here, we developed novel agonists for the other inhibitory receptor, killer immunoglobulin receptor (KIR), on NK cells. We found that antibodies that bind to activating KIR enhance NK cell activation and developed selective agonists for inhibitory KIRs (KIR2DL1, KIR2DL2/3, and KIR3DL1). Introducing these selective inhibitory KIR agonists on T cells and HLA class Ⅰ-deficient iPSCs allowed them to evade immune rejection by NK cells. Additionally, we identified an NKG2A-selective agonist as an alternative to chimeric HLA-E, which stimulates the activating receptor NKG2C. This technology enhances immune tolerance in allo-iPSCs and facilitates the development of various iPSC-derived regenerative medicines.

Indexed as

Killer Cells, NaturalNK Cell Lectin-Like Receptor Subfamily CReceptors, KIRGraft RejectionHistocompatibility Antigens Class IHumansInduced Pluripotent Stem CellsLymphocyte ActivationReceptors, KIR2DL1Receptors, KIR2DL2Receptors, KIR2DL3Receptors, KIR3DL1Histocompatibility Antigens Class IKIR2DL1 protein, humanKIR2DL2 protein, humanKIR2DL3 protein, humanKIR3DL1 protein, humanKLRC1 protein, humanNK Cell Lectin-Like Receptor Subfamily CReceptors, KIRReceptors, KIR2DL1Receptors, KIR2DL2Receptors, KIR2DL3Receptors, KIR3DL1

Identifiers

PMID41023081
PMCPMC12480839

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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.