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Updated: May 13, 2026
Ortho- and Ectopic Zebrafish Xeno-Engraftment of Ocular Melanoma to Recapitulate Primary Tumor and Experimental Metastasis Development
Published on: September 4, 2021
Decoding NY-ESO-1 TCR T cells: transcriptomic insights reveal dual mechanisms of tumor targeting in a melanoma murine
Alaa Alsalloum1,2, Saleh Alrhmoun1,2, Olga Perik-Zavosdkaia1
1Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.
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 CCR2 and CCR5, 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 in vivo 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.
Insights
Engineered T cells targeting NY-ESO-1 show potent anti-tumor effects in solid tumors. These T cells exhibit dual antigen-specific and NK-like responses for complete tumor eradication.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- T cell receptor-engineered T cells (TCR-T) show promise for solid tumors.
- Mechanisms of TCR-T cell efficacy against intracellular antigens are not fully understood.
Purpose of the Study:
- Investigate the functional state and mechanisms of TCR-T cells targeting NY-ESO-1 in solid tumors.
- Analyze the in vivo adaptation and antitumor responses of engineered T cells.
Main Methods:
- Retroviral vector-mediated TCR gene transfer.
- Flow cytometry, NanoString gene expression profiling, and single-cell RNA sequencing (scRNA-seq).
- SK-Mel-37 xenograft model for in vivo efficacy studies.
Main Results:
- Predominance of naive T cells with upregulated chemokine receptors (CCR2, CCR5) for enhanced tumor migration.
- Complete tumor eradication observed in the SK-Mel-37 xenograft model.
- Identification of CD8+ effector T cells with an NK cell-like gene expression profile via scRNA-seq.
Conclusions:
- NY-ESO-1 TCR-T cells demonstrate dual antitumor effects: antigen-specific CTL-like and antigen-independent NK-like responses.
- Engineered T cells possess versatile functional capabilities for potent tumor eradication.
- Findings support the therapeutic potential of NY-ESO-1 TCR-T cells for solid tumor treatment.
