Evidence map›Paper›PMID 41826286›Full record

ArticleSignal transduction and targeted therapy2026

Spatiotemporal profiling reveals distinct dynamics and checkpoint regulations of CAR-T and CAR-NKT cells against solid tumors.

Yan-Ruide Li, Miao Li, Yuning Chen, Houfu Leng, Yichen Zhu, Xinyuan Shen, Duncan Croll, Enbo Zhu, Jie Huang, Yu-Chen Wang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Signal transduction and targeted therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. 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.

Yan-Ruide Li *Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA. charlie.li@ucla.edu.ORCID http://orcid.org/0000-0002-9858-300X
Miao Li *Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Yuning Chen *Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Houfu LengDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Yichen ZhuDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Xinyuan ShenDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0009-0002-2788-3993
Duncan CrollDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Enbo ZhuDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Jie HuangDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Yu-Chen WangDepartment of Cardiovascular Surgery, First Affiliated Hospital of Anhui Medical University, and School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.
Abigail S KrallDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Heather R ChristofkDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Aldons J LusisDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-9013-0228
Lili YangDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA. liliyang@ucla.edu.

Funding

California Institute for Regenerative Medicine (CIRM) DISC2-11157California Institute for Regenerative Medicine (CIRM) DISC2-13015California Institute for Regenerative Medicine (CIRM) TRAN1-12250California Institute for Regenerative Medicine (CIRM) TRAN1-16050UC | University of California, Los Angeles (UCLA) CIRM-BSCRC Postdoctoral FellowshipUC | University of California, Los Angeles (UCLA) Goodman-Luskin Microbiome Center Collaborative Research Fellowship awardUC | University of California, Los Angeles (UCLA) UCLA BSCRC Innovation AwardUC | University of California, Los Angeles (UCLA) UCLA Chancellor's Award for Postdoctoral ResearchUC | University of California, Los Angeles (UCLA) UCLA Sydney Finegold Postdoctoral AwardU.S. Department of Defense (United States Department of Defense) CA200456
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapies have demonstrated remarkable efficacy in hematologic malignancies; however, their clinical performance in solid tumors remains limited due to suboptimal tumor infiltration, antigen heterogeneity, and immunosuppressive tumor microenvironments (TME). Invariant natural killer T (NKT) cells have recently emerged as a promising alternative platform for CAR engineering, owing to their intrinsic tissue-homing capacity, multi-modal cytotoxicity, and ability to reshape the TME. In this study, we performed a comprehensive preclinical comparison of conventional CAR-T cells and allogeneic stem cell-derived IL-15-enhanced CAR-NKT cells in solid tumor models, integrating spatiotemporal transcriptomic profiling across multiple tissues and longitudinal time points. Our analyses revealed distinct in vivo pharmacokinetic, pharmacodynamic, and immunoregulatory profiles between the two cell therapy modalities. Compared with CAR-T cells, CAR-NKT cells demonstrated superior homing, infiltration, and localization within solid tumors, along with prolonged in vivo persistence and a unique immune checkpoint receptor expression landscape. Notably, CAR-T cells exhibited synergistic antitumor responses when combined with TIGIT blockade, whereas CAR-NKT cells showed greater sensitivity to CD96 blockade in vivo. These findings highlight the divergent therapeutic dynamics of CAR-T and CAR-NKT cells and provide mechanistic insights that inform the rational design of next-generation cell therapies and combinatorial strategies for solid tumors.

Indexed as

Immunotherapy, AdoptiveNeoplasmsReceptors, Chimeric AntigenAnimalsCell Line, TumorHumansMiceTumor MicroenvironmentReceptors, Chimeric Antigen

Identifiers

PMID41826286
PMCPMC12987976

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.