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 let-7 miRNAs, the most p...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1462796/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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 let-7 miRNAs, the most prevalent family of miRNAs in lymphocytes. Recently it has been suggested that let-7 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 let-7 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 in vitro and in vivo. These findings highlight the intricate relationship between LIN28/let-7 axis and human T cell functionality, including in CAR T cell therapy. |
|---|---|
| ISSN: | 1664-3224 |