PXD031073 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | TRX1-enhanced CAR T cells retain their antitumor functions under pro-oxidative conditions |
Description | Immunotherapies with CAR-T cells achieve remarkable success, especially against B-cell malignancies. However, their activity against non-hematopoietic solid tumors is very limited. One central cause of this failure may be that a pro-oxidative tumor microenvironment can downmodulate the activation and migration of T-cells. In contrast to tumor cells, primary T cells have very low levels of antioxidants. This makes them prone to pro-oxidative effects. Oxidation-induced dysregulation of actin cytoskeletal dynamics hinders T-cell migration which allows only low tumor infiltration rates. In addition, the proliferation and the effector functions of T-cells (tumor cell killing) are disrupted. In order to strengthen human CAR-T cells against a pro-oxidative tumor microenvironment, we have increased increase their antioxidant capacity, e.g. by expressing antioxidants. We aimed to characterize the importance of antioxidant empowerment at functional level and at the molecular level. Among the antioxidant systems, thioredoxin1 (TRX1)-empowerment, allowed CAR T cells to retain their capacities for cytolytic immune synapse formation, cytokine release, proliferation, and cytotoxicity under pro-oxidative conditions. At the molecular level, gene expression analysis revealed that a pro-oxidative micromilieu caused a downmodulation of costimulatory and cytokine signals of T cells. One unique focus of this study was also to investigate global influence of reactive oxygen species on protein oxidation in T cells. Therefore, using TRX1 kinetic trapping and consequently mass spectrometry was employed to get insight into global oxidation levels in T cells. This analysis, namely redoxosome analysis, unveiled 196 oxidized proteins which were annotated to regulate several antitumor T cell functions. Taken together, our results provide evidence that TRX1 empowerment can increase CAR T cell efficacy against solid tumors. |
HostingRepository | PRIDE |
AnnounceDate | 2022-11-23 |
AnnouncementXML | Submission_2022-11-23_03:40:24.334.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | ThomasRuppert |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | N-ethylmaleimide derivatized cysteine; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-01-19 03:01:31 | ID requested | |
⏵ 1 | 2022-11-23 03:40:24 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: CAR T cells, ROS, immunosuppression, Thioredoxin 1,Cancer immunotherapy, redox regulation |
Contact List
ThomasRuppert |
contact affiliation | Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH) 69120 Heidelberg IM Neuenheimer Feld 282 69120 Heidelberg |
contact email | t.ruppert@zmbh.uni-heidelberg.de |
lab head | |
ThomasRuppert |
contact affiliation | ZMBH, Im Neuenheimer Feld 282, 69122 Heidelberg |
contact email | t.ruppert@zmbh.uni-heidelberg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD031073
- Label: PRIDE project
- Name: TRX1-enhanced CAR T cells retain their antitumor functions under pro-oxidative conditions