A new study published in Myeloid Cells (MC) reports that AS01, a vaccine adjuvant system best known for its use in AS01-adjuvanted vaccines, can induce trained immunity in human monocytes and reduce tumor growth in selected mouse cancer models.
Trained immunity refers to a form of long-term functional reprogramming in innate immune cells, enabling them to respond more strongly to later stimulation. In the study, researchers exposed human monocytes to AS01 and later challenged the cells with lipopolysaccharide. AS01-trained cells showed increased production of inflammatory cytokines, including IL-6 and TNF, after restimulation, suggesting enhanced innate immune responsiveness.
The researchers then tested AS01 in mouse models of melanoma, bladder cancer, and lung carcinoma. AS01 treatment reduced tumor growth in B16-F10 melanoma and MB49 bladder cancer models, while no comparable effect was observed in the Lewis lung carcinoma model. In responsive models, AS01 treatment was associated with changes in the tumor immune microenvironment, including increased frequencies of CD8+ T cells, neutrophils, and monocytes, together with a reduction in tumor-associated macrophages.
"These findings suggest that AS01 can induce a trained immunity phenotype and may have potential as a strategy to modulate antitumor immune responses," the authors report. The study also highlights the need for further research to clarify the mechanisms involved, determine why responses differ across tumor models, and evaluate whether this approach could eventually inform cancer immunotherapy development.
The authors emphasize that the findings are preclinical and should not be interpreted as evidence of therapeutic efficacy in patients. Further studies will be required before any clinical application can be considered.
