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

Pedro M. O. Ventura, Milica Gakovic, Berenice A. Fischer, Laura Spinelli, Giorgia Rota, Shalini Pathak, Hanif J. Khameneh, Alessandro Zenobi, Sarah Thomson, Walter Birchmeier, Doreen A. Cantrell (Lead / Corresponding author), Greta Guarda (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
61 Downloads (Pure)


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.

Original languageEnglish
Article numbere55399
Number of pages11
JournalEMBO Reports
Issue number11
Early online date4 Oct 2022
Publication statusPublished - 7 Nov 2022


  • PD-1 checkpoint blockade
  • Ptpn11
  • Ptpn6
  • T cell exhaustion
  • Cancer
  • Immunology
  • Signal Transduction

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry


Dive into the research topics of 'Concomitant deletion of Ptpn6 and Ptpn11 in T cells fails to improve anticancer responses'. Together they form a unique fingerprint.

Cite this