Concomitant deletion of Ptpn6 and Ptpn11 in T cells fails to improve anticancer responses.

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Date

7 novembre 2022

Type de document
Périmètre
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Source

Serveur académique Lausannois

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Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.15252/embr.202255399

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/36194675

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1469-3178

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_897F773196311

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Serveur Académique Lausannois

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Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/

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CD8-Positive T-Lymphocytes/metabolism; Programmed Cell Death 1 Receptor; Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics; Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism; Signal Transduction; PD-1 checkpoint blockade; Ptpn11; Ptpn6; T cell exhaustion

Sujets proches En

Thymus-dependent lymphocytes Thymus-derived cells T lymphocytes Thymus-dependent cells

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PMO Ventura et al., « Concomitant deletion of Ptpn6 and Ptpn11 in T cells fails to improve anticancer responses. », Serveur académique Lausannois, ID : 10.15252/embr.202255399

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Anticancer T cells acquire a dysfunctional state characterized by poor effector function and expression of inhibitory receptors, such as PD-1. Blockade of PD-1 leads to T cell reinvigoration and is increasingly applied as an effective anticancer treatment. Recent work challenged the commonly held view that the phosphatase PTPN11 (known as SHP-2) is essential for PD-1 signaling in T cells, suggesting functional redundancy with the homologous phosphatase PTPN6 (SHP-1). Therefore, we investigated the effect of concomitant Ptpn6 and Ptpn11 deletion in T cells on their ability to mount antitumour responses. In vivo data show that neither sustained nor acute Ptpn6/11 deletion improves T cell-mediated tumor control. Sustained loss of Ptpn6/11 also impairs the therapeutic effects of anti-PD1 treatment. In vitro results show that Ptpn6/11-deleted CD8 + T cells exhibit impaired expansion due to a survival defect and proteomics analyses reveal substantial alterations, including in apoptosis-related pathways. These data indicate that concomitant ablation of Ptpn6/11 in polyclonal T cells fails to improve their anticancer properties, implying that caution shall be taken when considering their inhibition for immunotherapeutic approaches.

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