Abstract A057: Metabolomic profiling reveals age-dependent metabolites that enhance CD8 T cell anti-tumor activity

Abstract The early life stage is a unique period, characterized by the presence of signaling molecules that differ from those in adults. Prior research has reported the suppression of aging and cellular reprogramming through the serum of young individuals, but specific information regarding the concrete factors is lacking. Recently, the importance of CD8+ T cell research has grown due to cancer immunotherapy. There is a current need for research on immune enhancement through the reprogramming of CD8+ T cells to overcome the limitations of existing treatments. In this study, we aim to establish a platform to identify the metabolites present in neonatal serum that can induce the reprogramming of CD8+ T cells, discover specific metabolites, and propose a new methodology for immunotherapy. Initially, we investigated in vitro CD8 T cell activation and chronic stimulation under CD3/CD28 engagement, using either adult or neonatal serum as the culture medium. Compared to CD8 T cells cultured with adult serum, those stimulated or chronically activated with neonatal serum exhibited enhanced cytotoxicity and proliferation. Next, metabolomic analysis was performed to identify metabolites enriched in neonatal serum that contribute to the enhanced CD8 T cell activation. Taurine, a substrate for the TAUT, was identified as an enriched metabolite in the neonatal serum. Therefore, we knocked down TAUT expression in CD8 T cells and subsequently activated them using either adult or neonatal serum. The TAUT knockdown cells showed significantly downregulated cytotoxicity even when stimulated with neonatal serum. Given Taurine's close association with the anti-oxidant system, NRF2 expression levels were investigated in neonatal serum-treated CD8 T cells, revealing an upregulation of NRF2. Subsequently, we investigated the in vivo effects of Taurine on tumor-infiltrating CD8 T cells by administering Taurine to a mouse tumor allograft model. In line with the in vitro results, tumors from Taurine-treated mice showed increased infiltration of CD8 T cells. Furthermore, these tumor-infiltrating CD8 T cells exhibited enhanced cytotoxicity and NRF2 expression. Collectively, these data suggest that Taurine, an enriched metabolite in neonatal serum, can rejuvenate adult CD8 T cell cytotoxicity and has the potential to be utilized as a potent booster for CD8 T cell-based cancer immunotherapy. Citation Format: Jongin Kim, Jin Soo Joo, Dongeun Lee, Jun Young Hong. Metabolomic profiling reveals age-dependent metabolites that enhance CD8 T cell anti-tumor activity [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A057.