Progressively Enhancing Stemness of Adoptively Transferred T Cells with PI3Kδ Blockade Improves Metabolism and Antitumor Immunity.

ABSTRACT: Generating stem-like memory T cells (TSCM) is a potential strategy to improve adoptive immunotherapy. Elucidating optimal ways to modulate signaling pathways that enrich TSCM properties could identify approaches to achieve this goal. We discovered herein that blocking the PI3Kδ pathway pharmaceutically to varying degrees can generate T cells with increasingly heightened stemness properties, based on the progressive enrichment of the transcription factors Tcf1 and Lef1. T cells with enhanced stemness features exhibited metabolic plasticity, marked by improved mitochondrial function and glucose uptake after tumor recognition. Conversely, T cells with low or medium stemness were less metabolically dynamic, vulnerable to antigen-induced cell death, and expressed more inhibitory checkpoint rece

SUBMITTER: Rangel Rivera GO 

PROVIDER: S-EPMC12147651 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature