DADA 增强 CD8(+) T 细胞干性以改善抗肿瘤免疫和免疫治疗疗效

Progenitor exhausted CD8 + T (Tpex) cells have recently been identified as a stem-like T cell subset that mediates durable anti-tumor immune responses and represents a pivotal population responsive to immunotherapies.

Here, it is demonstrated that diisopropylamine dichloroacetate (DADA) facilitates CD8 + T cell-mediated anti-tumor immunity and promotes Tpex cells accumulation in the tumor microenvironment.

Mechanistically, DADA promotes the conversion from pyruvate to Acetyl-CoA by inhibiting pyruvate dehydrogenase kinase. This process leads to increased oxidative phosphorylation (OXPHOS) and mitochondrial fitness, thereby enhancing CD8 + T cells stemness. Treatment of mice with DADA improves the efficacy of PD-1 blockade.

Furthermore, the in vitro expansion of chimeric antigen receptor (CAR)-T cells supplemented with DADA confers them with stemness characteristics, contributing to improved anti-tumor efficacy. Collectively, this study illustrates how DADA-mediated metabolic reprogramming in CD8 + T cell enhances their stemness, underscoring its potential for anti-tumor therapy.