Reprogramming CAR-T cells: Targeting SLC transporters for tumor microenvironment adaptation
T cell activation, triggered by antigen recognition via the T cell receptor, initiates crucial physiological changes necessary for proliferation and survival. This process encompasses epigenetic modifications that open chromatin for transcription factor binding, transcriptomic shifts activating key...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-10-01
|
| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825003536 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849222577855135744 |
|---|---|
| author | Beatriz Perucha Maialen Martinez-Tabar Inés Sanchez-Moreno Pedro Justicia Teresa Lozano Juan José Lasarte |
| author_facet | Beatriz Perucha Maialen Martinez-Tabar Inés Sanchez-Moreno Pedro Justicia Teresa Lozano Juan José Lasarte |
| author_sort | Beatriz Perucha |
| collection | DOAJ |
| description | T cell activation, triggered by antigen recognition via the T cell receptor, initiates crucial physiological changes necessary for proliferation and survival. This process encompasses epigenetic modifications that open chromatin for transcription factor binding, transcriptomic shifts activating key genes, and structural adaptations, including increased cell size and cytoskeletal changes. Activated T cells experience heightened metabolic demands, requiring efficient nutrient uptake primarily via Solute Carrier (SLC) transporters. These transporters, regulated by transcription factors such as c-Myc, HIF-1α, NF-κB, and mTORC1, optimize nutrient acquisition to support glycolysis and macromolecule synthesis. In the tumor microenvironment, however, aberrant tumor metabolism depletes nutrients and produces metabolites that impair T cell function and reduce the efficacy of adoptive cell therapies, which are not metabolically adapted to survive in such hostile conditions. Modulating SLC transporters presents a promising strategy to enhance chimeric antigen receptor T cell (CAR-T) effectiveness by improving their persistence and antitumor activity. Personalized approaches targeting SLC transporters, tailored to the metabolic profiles of specific tumor types, are crucial for maximizing the therapeutic potential of adoptive T cell therapies. This review explores the critical role of SLC transporters in CAR-T cell functionality and discusses strategies to optimize their expression and activity within the challenging TME. |
| format | Article |
| id | doaj-art-9c1b340138454870a5dd6978ecb121dc |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-9c1b340138454870a5dd6978ecb121dc2025-08-26T04:14:09ZengElsevierPharmacological Research1096-11862025-10-0122010792810.1016/j.phrs.2025.107928Reprogramming CAR-T cells: Targeting SLC transporters for tumor microenvironment adaptationBeatriz Perucha0Maialen Martinez-Tabar1Inés Sanchez-Moreno2Pedro Justicia3Teresa Lozano4Juan José Lasarte5Program of Immunology and Immunotherapy, Cima Universidad de Navarra, CCUN, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, CCUN, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, CCUN, Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, CCUN, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, SpainProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, CCUN, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; Corresponding authors at: Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.Program of Immunology and Immunotherapy, Cima Universidad de Navarra, CCUN, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; Corresponding authors at: Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.T cell activation, triggered by antigen recognition via the T cell receptor, initiates crucial physiological changes necessary for proliferation and survival. This process encompasses epigenetic modifications that open chromatin for transcription factor binding, transcriptomic shifts activating key genes, and structural adaptations, including increased cell size and cytoskeletal changes. Activated T cells experience heightened metabolic demands, requiring efficient nutrient uptake primarily via Solute Carrier (SLC) transporters. These transporters, regulated by transcription factors such as c-Myc, HIF-1α, NF-κB, and mTORC1, optimize nutrient acquisition to support glycolysis and macromolecule synthesis. In the tumor microenvironment, however, aberrant tumor metabolism depletes nutrients and produces metabolites that impair T cell function and reduce the efficacy of adoptive cell therapies, which are not metabolically adapted to survive in such hostile conditions. Modulating SLC transporters presents a promising strategy to enhance chimeric antigen receptor T cell (CAR-T) effectiveness by improving their persistence and antitumor activity. Personalized approaches targeting SLC transporters, tailored to the metabolic profiles of specific tumor types, are crucial for maximizing the therapeutic potential of adoptive T cell therapies. This review explores the critical role of SLC transporters in CAR-T cell functionality and discusses strategies to optimize their expression and activity within the challenging TME.http://www.sciencedirect.com/science/article/pii/S1043661825003536Solute carrier transportersTumor metabolismTumor microenvironmentImmunotherapyCAR-T cellsSolid tumors |
| spellingShingle | Beatriz Perucha Maialen Martinez-Tabar Inés Sanchez-Moreno Pedro Justicia Teresa Lozano Juan José Lasarte Reprogramming CAR-T cells: Targeting SLC transporters for tumor microenvironment adaptation Pharmacological Research Solute carrier transporters Tumor metabolism Tumor microenvironment Immunotherapy CAR-T cells Solid tumors |
| title | Reprogramming CAR-T cells: Targeting SLC transporters for tumor microenvironment adaptation |
| title_full | Reprogramming CAR-T cells: Targeting SLC transporters for tumor microenvironment adaptation |
| title_fullStr | Reprogramming CAR-T cells: Targeting SLC transporters for tumor microenvironment adaptation |
| title_full_unstemmed | Reprogramming CAR-T cells: Targeting SLC transporters for tumor microenvironment adaptation |
| title_short | Reprogramming CAR-T cells: Targeting SLC transporters for tumor microenvironment adaptation |
| title_sort | reprogramming car t cells targeting slc transporters for tumor microenvironment adaptation |
| topic | Solute carrier transporters Tumor metabolism Tumor microenvironment Immunotherapy CAR-T cells Solid tumors |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825003536 |
| work_keys_str_mv | AT beatrizperucha reprogrammingcartcellstargetingslctransportersfortumormicroenvironmentadaptation AT maialenmartineztabar reprogrammingcartcellstargetingslctransportersfortumormicroenvironmentadaptation AT inessanchezmoreno reprogrammingcartcellstargetingslctransportersfortumormicroenvironmentadaptation AT pedrojusticia reprogrammingcartcellstargetingslctransportersfortumormicroenvironmentadaptation AT teresalozano reprogrammingcartcellstargetingslctransportersfortumormicroenvironmentadaptation AT juanjoselasarte reprogrammingcartcellstargetingslctransportersfortumormicroenvironmentadaptation |