García-Rodriguez, PatriciaHidalgo, LauraRodriguez-Milla, Miguel ASomovilla-Crespo, BeatrizGarcia-Castro, Javier2024-11-212024-11-212024Front Immunol. 2024 Oct 16:15:1462796.https://hdl.handle.net/20.500.12105/25566LIN28, a highly conserved RNA-binding protein that acts as a posttranscriptional modulator, plays a vital role in the regulation of T-cell development, reprogramming, and immune activity in infectious diseases and T-cell-based immunotherapies. LIN28 inhibit the expression of miRNAs, the most prevalent family of miRNAs in lymphocytes. Recently it has been suggested that enhances murine anti-tumor immune responses. Here, we investigated the impact of LIN28 upregulation on human T cell functions, focusing on its influence on CAR T cell therapy. LIN28 lentiviral transduction of human T cells led to a stable expression of LIN28 that significantly downregulated the miRNA family without affecting cell viability or expansion potential. LIN28 overexpression maintained human T cell phenotype markers and functionality but impaired the antitumoral cytotoxicity of NKG2D-CAR T cells both and . These findings highlight the intricate relationship between LIN28/ axis and human T cell functionality, including in CAR T cell therapy.engVoRhttp://creativecommons.org/licenses/by/4.0/CAR TLIN28ImmunotherapyLet-7OsteosarcomaAnimalsCell Line, TumorCytotoxicity, ImmunologicHumansImmunotherapy, AdoptiveMiceMicroRNAsNK Cell Lectin-Like Receptor Subfamily KRNA-Binding ProteinsReceptors, Chimeric AntigenT-LymphocytesUp-RegulationXenograft Model Antitumor AssaysNeoplasmsAttribution 4.0 International3947886715146279610.3389/fimmu.2024.14627961664-3224Frontiers in immunologyopen access