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

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

Distinct Antiviral Properties of Two Different Bacterial Lysates

Oral bacterial lysates (OBLs) can reduce the frequency and severity of recurrent respiratory tract infections in children from viral and bacterial origins. OBL-induced early innate immune reaction was already shown, but the specific features of different OBLs have never been studied and compared. A study was conducted to assess in vitro the protective effects on rhinovirus- (RV-) infected human bronchial epithelial cells (BECs) of two slightly different OBLs: OM-85 and Pulmonarom. Furthermore, since immune cells represent the key arm for antiviral defence, the capacity of these OBLs to induce selected cytokine production in mouse bone marrow-derived DCs (BMDCs) was also evaluated. Although different OBLs may share some mechanisms to protect host cells from virus infection, some product-specific antimicrobial activities were observed on RV-infected human BECs and mouse BMDCs. These results are consistent with a product-specific response possibly triggered by different pathogen-associated molecular patterns (PAMPs) contained in OBLs