| First Author | Ventura PMO | Year | 2022 |
| Journal | EMBO Rep | Volume | 23 |
| Issue | 11 | Pages | e55399 |
| PubMed ID | 36194675 | Mgi Jnum | J:333063 |
| Mgi Id | MGI:7386670 | Doi | 10.15252/embr.202255399 |
| Citation | Ventura PMO, et al. (2022) Concomitant deletion of Ptpn6 and Ptpn11 in T cells fails to improve anticancer responses. EMBO Rep 23(11):e55399 |
| abstractText | 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. |
