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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1507218
This article is part of the Research Topic Novel Clinical and Translational Insights in Cell Therapies for Cancer View all 3 articles

Decoding NY-ESO-1 TCR T Cells: Transcriptomic Insights Reveal Dual Mechanisms of Tumor Targeting in a Melanoma Murine Xenograft Model

Provisionally accepted
Alaa Alsalloum Alaa Alsalloum 1,2Saleh Alrhmoun Saleh Alrhmoun 1,2Olga Perik-Zavodskaia Olga Perik-Zavodskaia 1Marina Fisher Marina Fisher 1Marina Volynets Marina Volynets 1Julia Lopatnikova Julia Lopatnikova 1Roman Perik-Zavodskii Roman Perik-Zavodskii 1Julia Shevchenko Julia Shevchenko 1Julia Philippova Julia Philippova 1Olga Solovieva Olga Solovieva 3Evgenii Zavjalov Evgenii Zavjalov 3Vasily Kurilin Vasily Kurilin 1Hiroshi Shiku Hiroshi Shiku 4Alexander Silkov Alexander Silkov 1Sergey Sennikov Sergey Sennikov 1,5*
  • 1 Research Institute of Fundamental and Clinical Immunology (RIFCI), Novosibirsk, Russia
  • 2 Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Novosibirsk Oblast, Russia
  • 3 Institute of Cytology and Genetics, Russian Academy of Sciences (RAS), Novosibirsk, Novosibirsk Oblast, Russia
  • 4 Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, Tsu 514-8507, Mie, Japan
  • 5 V. Zelman Institute for the Medicine and Psychology, Novosibirsk State UniversityRussia, Novosibirsk, Novosibirsk Oblast, Russia

The final, formatted version of the article will be published soon.

    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.

    Keywords: NY-ESO-1, cancer-testis antigen, TCR T cells, Adoptive Transfer, Xenograft, SK-Mel-37, mice model, Transcriptomics

    Received: 07 Oct 2024; Accepted: 08 Nov 2024.

    Copyright: © 2024 Alsalloum, Alrhmoun, Perik-Zavodskaia, Fisher, Volynets, Lopatnikova, Perik-Zavodskii, Shevchenko, Philippova, Solovieva, Zavjalov, Kurilin, Shiku, Silkov and Sennikov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sergey Sennikov, V. Zelman Institute for the Medicine and Psychology, Novosibirsk State UniversityRussia, Novosibirsk, 630090, Novosibirsk Oblast, Russia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.