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

Le résumé fourni par la source

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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.