Preclinical (aged mouse model + in vitro human cells) · PMID 41883056
IL-15 Plus Thymosin alpha1 Reduces Senescent Hepatic CD8+ T Cells in HCC via PI3K/AKT Suppression — VialBase Research
IL-15 + Ta1 combination suppressed tumor growth and prolonged survival in aged HCC mice
Last updated · 2026 · Wu F, Guo Z, Guan J, et al. · J Gastroenterol Hepatol
Key findings
- IL-15 + Ta1 combination suppressed tumor growth and prolonged survival in aged HCC mice
- Reduced senescent CD8+ T-cells while expanding activated effector populations
- Upregulated granzyme B, perforin, and IFN-gamma
- Mechanism: suppression of chronically overactivated PI3K/AKT signaling in hepatic CD8+ T-cells
- PI3K/AKT agonist SC79 abrogated therapeutic effects in vitro
IL-15 + Ta1 Reverses CD8+ Senescence in HCC (PMID: 41883056)
Study Design
- Orthotopic HCC model in aged C57BL/6 mice (22-26 months)
- Groups: saline, IL-15 alone, Ta1 alone, IL-15 + Ta1
- Monitoring: bioluminescence imaging, survival, flow cytometry, transcriptomics
- In vitro validation: human CD8+ T-cells co-cultured with Huh7 hepatoma cells
Key Results
- Combination therapy significantly suppressed tumor growth and prolonged survival
- Reduced senescent CD8+ T-cell proportion, expanded activated effectors
- Enhanced proliferative capacity and cytotoxic mediators (granzyme B, perforin, IFN-gamma)
- Attenuated chronically overactivated PI3K/AKT signaling
- SC79 (AKT agonist) abrogated effects, confirming pathway specificity
Mechanism Insight
Ta1 works by thymic rejuvenation (replenishing T-cell pool), while IL-15 rescues senescent CD8+ T-cells peripherally. The synergy targets PI3K/AKT — a pathway that becomes chronically overactivated in senescent T-cells, paradoxically impairing function.
Relevance
Supports Thymosin-Alpha-1 as an anti-immunosenescence agent. The IL-15 + Ta1 combination is a novel approach for age-related immune decline in cancer.
See Also
- Parent compound: Thymosin-Alpha-1