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...

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Bibliographic Details
Published in:Frontiers in immunology 2024-10, Vol.15, p.1462796
Main Authors: Garcia-Rodriguez, Patricia, Hidalgo, Laura, Rodriguez-Milla, Miguel Angel, Somovilla-Crespo, Beatriz, Garcia-Castro, Javier
Format: Article
Language:English
Subjects:
Animals
CAR T
Cell Line, Tumor
Cytotoxicity, Immunologic
Humans
Immunology
immunotherapy
Immunotherapy, Adoptive - methods
let-7
LIN28
Mice
MicroRNAs - genetics
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - therapy
NK Cell Lectin-Like Receptor Subfamily K - genetics
NK Cell Lectin-Like Receptor Subfamily K - metabolism
osteosarcoma
Receptors, Chimeric Antigen - genetics
Receptors, Chimeric Antigen - immunology
Receptors, Chimeric Antigen - metabolism
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Up-Regulation
Xenograft Model Antitumor Assays
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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 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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2024.1462796