Evidence map›Paper›PMID 39318093›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Single-cell RNA sequencing reveals anti-tumor potency of CD56

Wai Nam Liu, Sarah L Harden, Shawn Lu Wen Tan, Rachel Jun Rou Tan, Shin Yie Fong, Sue Yee Tan, Min Liu, Isha Karnik, Timothy Wai Ho Shuen, Han Chong Toh and 4 more

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Review
  2. Review
  3. CD49aScientific reports · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
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

14 authors.

Wai Nam LiuInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.
Sarah L HardenInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.
Shawn Lu Wen TanInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.
Rachel Jun Rou TanInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.
Shin Yie FongInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.
Sue Yee TanInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.
Min LiuInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.
Isha KarnikInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.
Timothy Wai Ho ShuenDivision of Medical Oncology, National Cancer Centre Singapore, Singapore 168583, Republic of Singapore.
Han Chong TohDivision of Medical Oncology, National Cancer Centre Singapore, Singapore 168583, Republic of Singapore.
Yong FanKey Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Seng Gee LimDivision of Gastroenterology and Hepatology, National University Hospital, Singapore 119228, Republic of Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.
Jerry Kok Yen ChanDepartment of Reproductive Medicine, KK Women's and Children's Hospital, Singapore 229899, Republic of Singapore; Experimental Fetal Medicine Group, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Republic of Singapore.
Qingfeng ChenInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A∗STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Republic of Singapore; Singapore Immunology Network (SIgN), A∗STAR, 8A Biomedical Grove, Immunos, Singapore 138648, Republic of Singapore. Electronic address: qchen@imcb.a-star.edu.sg.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In solid tumors, the exhaustion of natural killer (NK) cells and cytotoxic T cells in the immunosuppressive tumor microenvironment poses challenges for effective tumor control. Conventional humanized mouse models of hepatocellular carcinoma patient-derived xenografts (HCC-PDX) encounter limitations in NK cell infiltration, hindering studies on NK cell immunobiology. Here, we introduce an improved humanized mouse model with restored NK cell reconstitution and infiltration in HCC-PDX, coupled with single-cell RNA sequencing (scRNA-seq) to identify potential anti-HCC treatments. A single administration of adeno-associated virus carrying human interleukin-15 reinstated persistent NK cell reconstitution and infiltration in HCC-PDX in humanized mice. scRNA-seq revealed NK cell and T cell subpopulations with heightened PDCD1 and TIGIT levels. Notably, combination therapy with anti-PD-1 and anti-TIGIT antibodies alleviated HCC burden in humanized mice, demonstrating NK cell-dependent efficacy. Bulk-RNA sequencing analysis also revealed significant alterations in the tumor transcriptome that may contribute to further resistance after combination therapy, warranting further investigations. As an emerging strategy, ongoing clinical trials with anti-PD-1 and anti-TIGIT antibodies provide limited data. The improved humanized mouse HCC-PDX model not only sheds light on the pivotal role of NK cells but also serves as a robust platform for evaluating safety and anti-tumor efficacy of combination therapies and other potential regimens, complementing clinical insights.

Indexed as

Carcinoma, HepatocellularCD56 AntigenCD8-Positive T-LymphocytesKiller Cells, NaturalLiver NeoplasmsProgrammed Cell Death 1 ReceptorReceptors, ImmunologicAnimalsCell Line, TumorDependovirusDisease Models, AnimalHumansInterleukin-15MiceSequence Analysis, RNASingle-Cell AnalysisCD56 AntigenIL15 protein, humanInterleukin-15NCAM1 protein, humanPDCD1 protein, humanProgrammed Cell Death 1 ReceptorReceptors, ImmunologicTIGIT protein, humanhepatocellular carcinoma patient-derived xenograftshumanized miceimmune checkpoint inhibitorssingle-cell RNA sequencingtumor-infiltrating NK cellstumor-infiltrating T cells

Identifiers

PMID39318093
PMCPMC11573594

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.