Evidence map›Paper›PMID 42488650›Full record

ArticleFrontiers in immunology2026

Coexpression of GITRL confers resistance to Treg cell-mediated immunosuppression to anti-CD19 CAR-NK cells.

Dayane Schmidt, Sima Ebrahimabadi, Mariane Cariati Tirapelle, Camilly Melo Garcia Ferreira, Matheus Henrique Dos Santos, Alison Felipe Biggi, Mara Elisama da Silva Januário, Rodrigo Tocantins Calado, Virginia Picanço-Castro

Abstract read
In one paragraph

Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Dayane SchmidtCenter for Cell-based Therapy (CTC), Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Sima EbrahimabadiCenter for Cell-based Therapy (CTC), Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Mariane Cariati TirapelleCenter for Cell-based Therapy (CTC), Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Camilly Melo Garcia FerreiraCenter for Cell-based Therapy (CTC), Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Matheus Henrique Dos SantosCenter for Cell-based Therapy (CTC), Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Alison Felipe BiggiCenter for Cell-based Therapy (CTC), Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Mara Elisama da Silva JanuárioCenter for Cell-based Therapy (CTC), Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Rodrigo Tocantins CaladoCenter for Cell-based Therapy (CTC), Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Virginia Picanço-CastroCenter for Cell-based Therapy (CTC), Regional Blood Center of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Regulatory T cells play a pivotal role in shaping immune interactions, limiting antitumor immunity, and impairing the activity of engineered effector cells. Overcoming regulatory T (Treg) cell-mediated immunosuppression is critical to unlock the full therapeutic potential of chimeric antigen receptor (CAR)-cell therapies. Here, we develop "armored" anti-CD19 CAR-NK cells coexpressing GITR ligand (GITRL) (CAR19-GITRL-NK) to both target malignant B cells and locally counteract Treg-mediated suppression. GITR is highly expressed on Tregs, and engagement by its ligand GITRL can modulate their function, providing a rational strategy to reprogram the tumor microenvironment. Methods: We generated anti-CD19 NK-92 and primary peripheral blood NK (PB-NK) cells with or without GITRL coexpression using lentiviral vectors, and evaluated their functionality and therapeutic potential. CAR19-GITRL-NK-92 cells were analyzed regarding their expansion, metabolism, cytotoxicity, cytokine secretion, degranulation, and Results: CAR19-GITRL-NK-92 cells displayed superior expansion and enhanced metabolic fitness. Functionally, both CAR constructs increased the cytotoxicity of NK-92 and cytokine secretion against CD19⁺ Nalm-6 and Namalwa cells in vitro. RNA-Seq revealed 54 upregulated and 34 downregulated genes in CAR19-GITRL-NK-92 versus CAR19-NK-92 cells, with enrichment of pathways linked to immune activation, proliferation, chemotaxis, and cytotoxicity, including increased expression of NCR2, CD2, CMKLR1, IRF5, KIT, and PTPN3. Discussion: Collectively, these data position CAR19-GITRL-NK cells as a potent and innovative strategy that couples direct tumor targeting with active undermining of Treg-driven immunosuppression for the treatment of B-cell leukemias and lymphomas.

Indexed as

Antigens, CD19Glucocorticoid-Induced TNFR-Related ProteinImmunotherapy, AdoptiveKiller Cells, NaturalReceptors, Chimeric AntigenT-Lymphocytes, RegulatoryTumor Necrosis FactorsAnimalsCytotoxicity, ImmunologicHumansImmune ToleranceMiceAntigens, CD19Glucocorticoid-Induced TNFR-Related ProteinReceptors, Chimeric AntigenTNFRSF18 protein, humanTNFSF18 protein, humanTumor Necrosis FactorsB-Cell MalignancyCAR-NK CellsChimeric Antigen ReceptorGITRLImmunotherapyTreg cells

Identifiers

PMID42488650
PMCPMC13389840

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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.