Transient EZH2 Suppression by Tazemetostat during In Vitro Expansion Maintains T-Cell Stemness and Improves Adoptive T-Cell Therapy.

The histone methyltransferase enhancer of zeste homolog 2 (EZH2) plays important roles in T-cell differentiation, proliferation, and function. Previous studies have demonstrated that genetic deletion of EZH2 in CD8+ or total T cells impairs their antiviral and antitumor activities, cytokine production, and ability to expand upon rechallenge. Contrary to the detrimental role of deleting T cell-intrinsic EZH2, in this study, we demonstrated that transient inhibition of EZH2 in T cells prior to the phenotypic onset of exhaustion with a clinically approved inhibitor, tazemetostat (Taz), delayed their dysfunctional progression and preserved T-cell stemness and polyfunctionality but had no negative impact on cell proliferation.

Characteristics that increase the risk for pain on propofol injection.

Background: Propofol for anesthesia has become increasingly popular for endoscopic procedures. However, pain on propofol injection (POPI) remains an issue with administration. The primary endpoint of this study was to identify patient characteristics and factors, such as IV site and gauge, that could predict the occurrence of POPI.

Diabetes as a consequence of acute pancreatitis.

Diabetes is a highly prevalent disease that was initially simplified into three major types: Type 1, type 2 and gestational diabetes. With the global rise in incidence of acute pancreatitis (AP), a lesser-known type of diabetes referred to as diabetes of the exocrine pancreas (DEP) is becoming more recognized. However, there is a poor understanding of the inherent relationship between diabetes and AP.

Chemoenzymatic Measurement of LacNAc in Single-Cell Multiomics Reveals It as a Cell-Surface Indicator of Glycolytic Activity of CD8 T Cells.

Despite the rich information about the physiological state of a cell encoded in the dynamic changes of cell-surface glycans, chemical methods to capture specific glycan epitopes at the single-cell level are quite limited. Here, we report a chemoenzymatic method for the single-cell detection of N-acetyllactosamine (LacNAc) by labeling LacNAc with a specific DNA barcode. The chemoenzymatic labeling does not alter the transcriptional status of immune cells and is compatible with multiple scRNA-seq platforms.

Transient EZH2 suppression by Tazemetostat during expansion maintains T cell stemness and improves adoptive T cell therapy.

The histone methyltransferase enhancer of zeste homolog 2 (EZH2)-mediated epigenetic regulation of T cell differentiation in acute infection has been extensively investigated. However, the role of EZH2 in T cell exhaustion remains under-explored. Here, using exhaustion models, we demonstrated that transient inhibition of EZH2 in T cells before the phenotypic onset of exhaustion with a clinically approved inhibitor, Tazemetastat, delayed their dysfunctional progression and maintained T cell stemness and polyfunctionality while having no negative impact on cell proliferation.