LIN28 upregulation in primary human T cells impaired CAR T antitumoral activity
LIN28, 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 prevale...
| Autores: | ; ; ; ; |
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| Tipo de documento: | Artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Lenguaje: | Inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/25566 |
| Acceso en línea: | https://hdl.handle.net/20.500.12105/25566 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | CAR T LIN28 Immunotherapy Let-7 Osteosarcoma Animals Cell Line, Tumor Cytotoxicity, Immunologic Humans Immunotherapy, Adoptive Mice MicroRNAs NK Cell Lectin-Like Receptor Subfamily K RNA-Binding Proteins Receptors, Chimeric Antigen T-Lymphocytes Up-Regulation Xenograft Model Antitumor Assays Neoplasms |
| Sumario: | LIN28, 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. |
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