PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells

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Flosbach, M; Oberle, SG; Scherer, S; Zecha, J; von Hoesslin, M; Wiede, F; Chennupati, V; Cullen, JG; List, M; Pauling, JK; ...Date
2020-07-28Source Title
Cell ReportsPublisher
CELL PRESSAffiliation
Sir Peter MacCallum Department of OncologyMetadata
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Journal ArticleCitations
Flosbach, M., Oberle, S. G., Scherer, S., Zecha, J., von Hoesslin, M., Wiede, F., Chennupati, V., Cullen, J. G., List, M., Pauling, J. K., Baumbach, J., Kuster, B., Tiganis, T. & Zehn, D. (2020). PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells. CELL REPORTS, 32 (4), https://doi.org/10.1016/j.celrep.2020.107957.Access Status
Open AccessAbstract
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.
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