Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer
Identification of human cancer-reactive CD8+ T cells is crucial for the stratification of patients for immunotherapy and determination of immune-therapeutic effects. To date, these T cells have been identified mainly based on cell surface expression of programmed cell death protein 1 (PD-1) or co-ex...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/8/1924 |
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| author | Joyce M. Lubbers Marta A. Ważyńska Nienke van Rooij Arjan Kol Hagma H. Workel Annechien Plat Sterre T. Paijens Martijn R. Vlaming Diana C. J. Spierings Philip H. Elsinga Edwin Bremer Hans W. Nijman Marco de Bruyn |
| author_facet | Joyce M. Lubbers Marta A. Ważyńska Nienke van Rooij Arjan Kol Hagma H. Workel Annechien Plat Sterre T. Paijens Martijn R. Vlaming Diana C. J. Spierings Philip H. Elsinga Edwin Bremer Hans W. Nijman Marco de Bruyn |
| author_sort | Joyce M. Lubbers |
| collection | DOAJ |
| description | Identification of human cancer-reactive CD8+ T cells is crucial for the stratification of patients for immunotherapy and determination of immune-therapeutic effects. To date, these T cells have been identified mainly based on cell surface expression of programmed cell death protein 1 (PD-1) or co-expression of CD103 and CD39. A small subset of CD103− CD39+ CD8+ T cells is also present in tumors, but little is known about these T cells. Here, we report that CD103− CD39+ CD8+ T cells from mismatch repair-deficient endometrial tumors are activated and characterized predominantly by expression of <i>TNFRSF9</i>. In vitro, transforming growth factor-beta (TGF-β) drives the disappearance of this subset, likely through the conversion of CD103− CD39+ cells to a CD103+ phenotype. On the transcriptomic level, T cell activation and induction of CD39 was associated with a number of tissue residence and TGF-β responsive transcription factors. Altogether, our data suggest CD39+ CD103− CD8+ tumor-infiltrating T cells are recently activated and likely rapidly differentiate towards tissue residence upon exposure to TGF-β in the tumor micro-environment, explaining their relative paucity in human tumors. |
| first_indexed | 2024-03-09T11:03:32Z |
| format | Article |
| id | doaj.art-bb6741a5c186465885e60426cf214bbe |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T11:03:32Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bb6741a5c186465885e60426cf214bbe2023-12-01T01:05:55ZengMDPI AGCancers2072-66942022-04-01148192410.3390/cancers14081924Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial CancerJoyce M. Lubbers0Marta A. Ważyńska1Nienke van Rooij2Arjan Kol3Hagma H. Workel4Annechien Plat5Sterre T. Paijens6Martijn R. Vlaming7Diana C. J. Spierings8Philip H. Elsinga9Edwin Bremer10Hans W. Nijman11Marco de Bruyn12Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsEuropean Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsIdentification of human cancer-reactive CD8+ T cells is crucial for the stratification of patients for immunotherapy and determination of immune-therapeutic effects. To date, these T cells have been identified mainly based on cell surface expression of programmed cell death protein 1 (PD-1) or co-expression of CD103 and CD39. A small subset of CD103− CD39+ CD8+ T cells is also present in tumors, but little is known about these T cells. Here, we report that CD103− CD39+ CD8+ T cells from mismatch repair-deficient endometrial tumors are activated and characterized predominantly by expression of <i>TNFRSF9</i>. In vitro, transforming growth factor-beta (TGF-β) drives the disappearance of this subset, likely through the conversion of CD103− CD39+ cells to a CD103+ phenotype. On the transcriptomic level, T cell activation and induction of CD39 was associated with a number of tissue residence and TGF-β responsive transcription factors. Altogether, our data suggest CD39+ CD103− CD8+ tumor-infiltrating T cells are recently activated and likely rapidly differentiate towards tissue residence upon exposure to TGF-β in the tumor micro-environment, explaining their relative paucity in human tumors.https://www.mdpi.com/2072-6694/14/8/1924CD103CD39PD-1TGF-βexhaustion |
| spellingShingle | Joyce M. Lubbers Marta A. Ważyńska Nienke van Rooij Arjan Kol Hagma H. Workel Annechien Plat Sterre T. Paijens Martijn R. Vlaming Diana C. J. Spierings Philip H. Elsinga Edwin Bremer Hans W. Nijman Marco de Bruyn Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer Cancers CD103 CD39 PD-1 TGF-β exhaustion |
| title | Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer |
| title_full | Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer |
| title_fullStr | Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer |
| title_full_unstemmed | Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer |
| title_short | Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer |
| title_sort | expression of cd39 identifies activated intratumoral cd8 t cells in mismatch repair deficient endometrial cancer |
| topic | CD103 CD39 PD-1 TGF-β exhaustion |
| url | https://www.mdpi.com/2072-6694/14/8/1924 |
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