Cellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, Spain.
Universidad Nacional de Educación a (UNED), Madrid, Spain.
Front Immunol. 2024 Oct 16;15:1462796. doi: 10.3389/fimmu.2024.1462796. eCollection 2024.
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.
LIN28 是一种高度保守的 RNA 结合蛋白，作为一种转录后调节剂，在 T 细胞发育、重编程以及传染病和基于 T 细胞的免疫疗法中的免疫活性的调节中起着至关重要的作用。LIN28 抑制 miRNA 的表达，miRNA 是淋巴细胞中最普遍的 miRNA 家族。最近有研究表明，LIN28 增强了小鼠的抗肿瘤免疫反应。在这里，我们研究了 LIN28 上调对人 T 细胞功能的影响，重点研究了它对嵌合抗原受体 T 细胞（CAR T 细胞）治疗的影响。LIN28 慢病毒转导人 T 细胞导致 LIN28 的稳定表达，显著下调 miRNA 家族，而不影响细胞活力或扩增潜力。LIN28 的过表达维持了人 T 细胞表型标志物和功能，但损害了 NKG2D-CAR T 细胞的抗肿瘤细胞毒性 both 和 。这些发现强调了 LIN28/轴与人类 T 细胞功能之间的复杂关系，包括在 CAR T 细胞治疗中。
