PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells
Summary: Manipulating molecules that impact T cell receptor (TCR) or cytokine signaling, such as the protein tyrosine phosphatase non-receptor type 2 (PTPN2), has significant potential for advancing T cell-based immunotherapies. Nonetheless, it remains unclear how PTPN2 impacts the activation, survi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720309384 |
| _version_ | 1818448149615738880 |
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| author | Markus Flosbach Susanne G. Oberle Stefanie Scherer Jana Zecha Madlaina von Hoesslin Florian Wiede Vijaykumar Chennupati Jolie G. Cullen Markus List Josch K. Pauling Jan Baumbach Bernhard Kuster Tony Tiganis Dietmar Zehn |
| author_facet | Markus Flosbach Susanne G. Oberle Stefanie Scherer Jana Zecha Madlaina von Hoesslin Florian Wiede Vijaykumar Chennupati Jolie G. Cullen Markus List Josch K. Pauling Jan Baumbach Bernhard Kuster Tony Tiganis Dietmar Zehn |
| author_sort | Markus Flosbach |
| collection | DOAJ |
| description | Summary: Manipulating molecules that impact T cell receptor (TCR) or cytokine signaling, such as the protein tyrosine phosphatase non-receptor type 2 (PTPN2), has significant potential for advancing T cell-based immunotherapies. Nonetheless, it remains unclear how PTPN2 impacts the activation, survival, and memory formation of T cells. We find that PTPN2 deficiency renders cells in vivo and in vitro less dependent on survival-promoting cytokines, such as interleukin (IL)-2 and IL-15. Remarkably, briefly ex vivo-activated PTPN2-deficient T cells accumulate in 3- to 11-fold higher numbers following transfer into unmanipulated, antigen-free mice. Moreover, the absence of PTPN2 augments the survival of short-lived effector T cells and allows them to robustly re-expand upon secondary challenge. Importantly, we find no evidence for impaired effector function or memory formation. Mechanistically, PTPN2 deficiency causes broad changes in the expression and phosphorylation of T cell expansion and survival-associated proteins. Altogether, our data underline the therapeutic potential of targeting PTPN2 in T cell-based therapies to augment the number and survival capacity of antigen-specific T cells. |
| first_indexed | 2024-12-14T20:14:55Z |
| format | Article |
| id | doaj.art-b80b51dab21742a387dd709797f00701 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-14T20:14:55Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b80b51dab21742a387dd709797f007012022-12-21T22:48:52ZengElsevierCell Reports2211-12472020-07-01324107957PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T CellsMarkus Flosbach0Susanne G. Oberle1Stefanie Scherer2Jana Zecha3Madlaina von Hoesslin4Florian Wiede5Vijaykumar Chennupati6Jolie G. Cullen7Markus List8Josch K. Pauling9Jan Baumbach10Bernhard Kuster11Tony Tiganis12Dietmar Zehn13Division of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, GermanyDivision of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, SwitzerlandDivision of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, Germany; Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, SwitzerlandChair of Proteomics and Bioanalytics, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, GermanyDivision of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, GermanyDepartment of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Peter MacCallum Cancer Centre, Melbourne, VIC 3000, AustraliaDivision of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, SwitzerlandDivision of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, GermanyBig Data in BioMedicine Group, Chair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, GermanyZD.B Junior Research Group LipiTUM, Chair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, GermanyChair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, GermanyChair of Proteomics and Bioanalytics, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, GermanyDepartment of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, AustraliaDivision of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich (TUM), Freising, Germany; Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Corresponding authorSummary: Manipulating molecules that impact T cell receptor (TCR) or cytokine signaling, such as the protein tyrosine phosphatase non-receptor type 2 (PTPN2), has significant potential for advancing T cell-based immunotherapies. Nonetheless, it remains unclear how PTPN2 impacts the activation, survival, and memory formation of T cells. We find that PTPN2 deficiency renders cells in vivo and in vitro less dependent on survival-promoting cytokines, such as interleukin (IL)-2 and IL-15. Remarkably, briefly ex vivo-activated PTPN2-deficient T cells accumulate in 3- to 11-fold higher numbers following transfer into unmanipulated, antigen-free mice. Moreover, the absence of PTPN2 augments the survival of short-lived effector T cells and allows them to robustly re-expand upon secondary challenge. Importantly, we find no evidence for impaired effector function or memory formation. Mechanistically, PTPN2 deficiency causes broad changes in the expression and phosphorylation of T cell expansion and survival-associated proteins. Altogether, our data underline the therapeutic potential of targeting PTPN2 in T cell-based therapies to augment the number and survival capacity of antigen-specific T cells.http://www.sciencedirect.com/science/article/pii/S2211124720309384Protein tyrosine phosphatase non‑receptor type 2 (PTPN2)T cell memoryprogrammed T cell expansionadoptive T cell transferimmunotherapyeffector T cells |
| spellingShingle | Markus Flosbach Susanne G. Oberle Stefanie Scherer Jana Zecha Madlaina von Hoesslin Florian Wiede Vijaykumar Chennupati Jolie G. Cullen Markus List Josch K. Pauling Jan Baumbach Bernhard Kuster Tony Tiganis Dietmar Zehn PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells Cell Reports Protein tyrosine phosphatase non‑receptor type 2 (PTPN2) T cell memory programmed T cell expansion adoptive T cell transfer immunotherapy effector T cells |
| title | PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells |
| title_full | PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells |
| title_fullStr | PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells |
| title_full_unstemmed | PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells |
| title_short | PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells |
| title_sort | ptpn2 deficiency enhances programmed t cell expansion and survival capacity of activated t cells |
| topic | Protein tyrosine phosphatase non‑receptor type 2 (PTPN2) T cell memory programmed T cell expansion adoptive T cell transfer immunotherapy effector T cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720309384 |
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