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Decoding NY-ESO-1 TCR T cells: transcriptomic insights reveal dual mechanisms of tumor targeting in a melanoma murine xenograft model.

作者信息

Alsalloum Alaa, Alrhmoun Saleh, Perik-Zavosdkaia Olga, Fisher Marina, Volynets Marina, Lopatnikova Julia, Perik-Zavodskii Roman, Shevchenko Julia, Philippova Julia, Solovieva Olga, Zavjalov Evgenii, Kurilin Vasily, Shiku Hiroshi, Silkov Alexander, Sennikov Sergey

机构信息

Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.

Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia.

出版信息

Front Immunol. 2024 Nov 26;15:1507218. doi: 10.3389/fimmu.2024.1507218. eCollection 2024.


DOI:10.3389/fimmu.2024.1507218
PMID:39660132
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11628372/
Abstract

The development of T cell receptor-engineered T cells (TCR-T) targeting intracellular antigens is a promising strategy for treating solid tumors; however, the mechanisms underlying their effectiveness remain poorly understood. In this study, we employed advanced techniques to investigate the functional state of T cells engineered with retroviral vectors to express a TCR specific for the NY-ESO-1 157-165 peptide in the HLA-A*02:01 context. Flow cytometry revealed a predominance of naïve T cells. Gene expression profiling using NanoString technology revealed upregulation of genes encoding chemokine receptors and , indicating enhanced migration towards tumor sites. In the SK-Mel-37 xenograft model, these transduced T cells achieved complete tumor eradication. Furthermore, single-cell RNA sequencing (scRNA-seq) conducted 14 days post-TCR T cell infusion provided a comprehensive analysis of the adaptation of these cells, identifying a distinct subset of CD8+ effector T cells with an NK cell-like gene expression profile. Our findings indicate that NY-ESO-1 TCR-transduced T cells have the potential to mediate dual antitumor effects through both antigen-independent NK-like and antigen-specific CTL-like responses. This study underscores the potential of NY-ESO-1 TCR-T cells as potent tumor-eradicating agents, highlighting the importance of harnessing their versatile functional capabilities to refine and enhance therapeutic strategies.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b8/11628372/19fe8ae91016/fimmu-15-1507218-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b8/11628372/f6d49eebee59/fimmu-15-1507218-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b8/11628372/2b75aed85526/fimmu-15-1507218-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b8/11628372/2980e71494b8/fimmu-15-1507218-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b8/11628372/19fe8ae91016/fimmu-15-1507218-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b8/11628372/f6d49eebee59/fimmu-15-1507218-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b8/11628372/2b75aed85526/fimmu-15-1507218-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b8/11628372/2980e71494b8/fimmu-15-1507218-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b8/11628372/19fe8ae91016/fimmu-15-1507218-g004.jpg

相似文献

[1]
Decoding NY-ESO-1 TCR T cells: transcriptomic insights reveal dual mechanisms of tumor targeting in a melanoma murine xenograft model.

Front Immunol. 2024-11-26

[2]
Generation and characterization of HLA-A2 transgenic mice expressing the human TCR 1G4 specific for the HLA-A2 restricted NY-ESO-1 tumor-specific peptide.

J Immunother Cancer. 2021-6

[3]
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[4]
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[5]
A rare population of tumor antigen-specific CD4CD8 double-positive αβ T lymphocytes uniquely provide CD8-independent TCR genes for engineering therapeutic T cells.

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[6]
A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response.

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[7]
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[8]
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[9]
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[10]
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[1]
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Front Immunol. 2025-7-11

[2]
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[3]
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本文引用的文献

[1]
NY-ESO-1 antigen: A promising frontier in cancer immunotherapy.

Clin Transl Med. 2024-9

[2]
TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against Tumors.

Biomedicines. 2023-10-16

[3]
Advances in single-cell RNA sequencing and its applications in cancer research.

J Hematol Oncol. 2023-8-24

[4]
T-BET and EOMES sustain mature human NK cell identity and antitumor function.

J Clin Invest. 2023-7-3

[5]
Dictionary learning for integrative, multimodal and scalable single-cell analysis.

Nat Biotechnol. 2024-2

[6]
CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances.

Mol Cancer. 2023-1-30

[7]
Early T-bet promotes LFA1 upregulation required for CD8+ effector and memory T cell development.

J Exp Med. 2023-2-6

[8]
GSEApy: a comprehensive package for performing gene set enrichment analysis in Python.

Bioinformatics. 2023-1-1

[9]
Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours.

Nat Rev Clin Oncol. 2023-1

[10]
NKG7 Is Required for Optimal Antitumor T-cell Immunity.

Cancer Immunol Res. 2022-2

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