Evidence map›Paper›PMID 41587986›Full record

ArticleNature communications2026

CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting.

Ari Itoh-Nakadai, Minggao Liang, Michiho Shindo, Chen Bibi, Mariko Tomizawa-Murasawa, Saera Fujiki, Akiko Kaneko, Emi Kanamaru, Mari Hashimoto, Hiroshi Kajita and 32 more

Abstract read
In one paragraph

Article in Nature communications, 2026. 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. Review
  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

42 authors.

Ari Itoh-Nakadai *Laboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Minggao Liang *Laboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Michiho ShindoLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Chen BibiLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Mariko Tomizawa-MurasawaLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Saera FujikiLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Akiko KanekoLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Emi KanamaruLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.ORCID http://orcid.org/0009-0002-9575-2127
Mari HashimotoLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Hiroshi KajitaLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Yoshinari AndoLaboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.ORCID http://orcid.org/0000-0002-8128-6201
Miki KojimaLaboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.ORCID http://orcid.org/0000-0003-2295-2873
Jonathan MoodyLaboratory for Genome Information Analysis, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.ORCID http://orcid.org/0000-0001-9261-711X
Makoto IwasakiLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.ORCID http://orcid.org/0000-0002-7564-157X
Shinsuke TakagiDepartment of Hematology, Toranomon Hospital, Tokyo, Japan.ORCID http://orcid.org/0000-0003-0441-393X
Ryo NakagawaLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Saumya AgrawalLaboratory for Applied Computational Genomics, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.
Hanae Amitani-IijimaLaboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.
Kaori SatoLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Yuriko SorimachiDepartment of Stem Cell Biology, National Institute of Global Health and Medicine, Japan Institute for Health Security (JIHS), Tokyo, Japan.
Nahoko SuzukiLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Takehiro FukamiLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Kazuharu HanadaDrug Discovery Structural Biology Platform Unit, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.
Satoshi MoritaDrug Discovery Structural Biology Platform Unit, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.
Kazushige KatsuraDrug Discovery Structural Biology Platform Unit, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.ORCID http://orcid.org/0000-0002-4333-0224
Takehisa MatsumotoDrug Discovery Structural Biology Platform Unit, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.
Maiko KobayashiDepartment of Hygiene and Public Health, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Masahiko KatoDepartment of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan.
Yasuyuki NegishiDepartment of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan.
Mikako ShirouzuDrug Discovery Structural Biology Platform Unit, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.ORCID http://orcid.org/0000-0002-7997-2149
Yuho NajimaHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.ORCID http://orcid.org/0000-0001-8910-0021
Keiyo TakuboDepartment of Stem Cell Biology, National Institute of Global Health and Medicine, Japan Institute for Health Security (JIHS), Tokyo, Japan.ORCID http://orcid.org/0000-0002-1736-7592
Chung Chau HonLaboratory for Genome Information Analysis, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.
Naoyuki UchidaDepartment of Hematology, Toranomon Hospital, Tokyo, Japan.ORCID http://orcid.org/0000-0001-5952-5926
Shuichi TaniguchiDepartment of Hematology, Toranomon Hospital, Tokyo, Japan.
Yukihide MomozawaLaboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.
Piero CarninciLaboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.ORCID http://orcid.org/0000-0001-7202-7243
Leonard D ShultzThe Jackson Laboratory, Bar Harbor, ME, USA.
Yoriko SaitoLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan.
Michiel de HoonLaboratory for Applied Computational Genomics, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.ORCID http://orcid.org/0000-0003-0489-2352
Jay W ShinLaboratory for Advanced Genomics Circuit, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.ORCID http://orcid.org/0000-0003-4037-3533
Fumihiko IshikawaLaboratory for Human Disease Models, RIKEN Center for Integrative Medical Sciences, RIKEN, Kanagawa, Japan. fumihiko.ishikawa@riken.jp.ORCID http://orcid.org/0000-0002-8717-1237

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI Paul Robson · 1985 to 2026
$61.9M
MEXT | Japan Society for the Promotion of Science (JSPS) 22F22072MEXT | Japan Society for the Promotion of Science (JSPS) 22H04925MEXT | Japan Society for the Promotion of Science (JSPS) 22H04997NCI NIH HHS P30 CA034196Secom Science and Technology Foundation (SSTF) 2025
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B-cell malignancies, but its success in acute myeloid leukemia (AML) remains limited. Durable responses depend on the formation of long-lived memory T cells, whereas T cell exhaustion contributes to non-response and relapse. In patients with AML who achieved remission after cord blood transplantation, we here first observe enrichment of memory T cells with high expression of the chemokine receptor CXCR4. Next, we show that engineering CAR-T cells to co-express CXCR4 enhances their persistence and anti-leukemic activity in patient-derived xenograft models. Using single-cell profiling and metabolic analysis, we find that CXCR4 promotes memory-associated transcriptional programs, reduces exhaustion, and supports oxidative metabolism. These effects are observed with CAR-T cells targeting CD25 or CD96 as AML-associated targets. Our results indicate that CXCR4 strengthens CAR-T cell memory and durability, offering a strategy to improve immunotherapy outcomes in AML and beyond.

Indexed as

Immunologic MemoryImmunotherapy, AdoptiveLeukemia, Myeloid, AcuteMemory T CellsReceptors, Chimeric AntigenReceptors, CXCR4AnimalsCell Line, TumorFemaleHumansMiceT-Cell ExhaustionT-LymphocytesXenograft Model Antitumor AssaysCXCR4 protein, humanReceptors, Chimeric AntigenReceptors, CXCR4

Identifiers

PMID41587986
PMCPMC12835132

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LicenceCC BY-NC-ND
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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.