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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1462796/full |
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| author | Patricia Garcia-Rodriguez Patricia Garcia-Rodriguez Laura Hidalgo Miguel Angel Rodriguez-Milla Beatriz Somovilla-Crespo Javier Garcia-Castro Javier Garcia-Castro |
| author_facet | Patricia Garcia-Rodriguez Patricia Garcia-Rodriguez Laura Hidalgo Miguel Angel Rodriguez-Milla Beatriz Somovilla-Crespo Javier Garcia-Castro Javier Garcia-Castro |
| author_sort | Patricia Garcia-Rodriguez |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-89d80d6b3c594a39b5f7cbec3a69c473 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-89d80d6b3c594a39b5f7cbec3a69c4732025-08-20T01:47:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-10-011510.3389/fimmu.2024.14627961462796LIN28 upregulation in primary human T cells impaired CAR T antitumoral activityPatricia Garcia-Rodriguez0Patricia Garcia-Rodriguez1Laura Hidalgo2Miguel Angel Rodriguez-Milla3Beatriz Somovilla-Crespo4Javier Garcia-Castro5Javier Garcia-Castro6Cellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, SpainUniversidad Nacional de Educación a (UNED), Madrid, SpainCellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, SpainCellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, SpainCellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, SpainCellular Biotechnology Unit, Instituto de Salud Carlos III, Madrid, SpainInstituto de Investigación de Enfermedades Raras (IIER) & Departamento de Desarrollo de Medicamentos de Terapias Avanzadas (DDMTA), Instituto de Salud Carlos III, Madrid, SpainLIN28, 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1462796/fullLIN28let-7CAR Timmunotherapyosteosarcoma |
| spellingShingle | Patricia Garcia-Rodriguez Patricia Garcia-Rodriguez Laura Hidalgo Miguel Angel Rodriguez-Milla Beatriz Somovilla-Crespo Javier Garcia-Castro Javier Garcia-Castro LIN28 upregulation in primary human T cells impaired CAR T antitumoral activity Frontiers in Immunology LIN28 let-7 CAR T immunotherapy osteosarcoma |
| title | LIN28 upregulation in primary human T cells impaired CAR T antitumoral activity |
| title_full | LIN28 upregulation in primary human T cells impaired CAR T antitumoral activity |
| title_fullStr | LIN28 upregulation in primary human T cells impaired CAR T antitumoral activity |
| title_full_unstemmed | LIN28 upregulation in primary human T cells impaired CAR T antitumoral activity |
| title_short | LIN28 upregulation in primary human T cells impaired CAR T antitumoral activity |
| title_sort | lin28 upregulation in primary human t cells impaired car t antitumoral activity |
| topic | LIN28 let-7 CAR T immunotherapy osteosarcoma |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1462796/full |
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