| Popis: |
CD8+ T-cells play a critical role in anti-tumour immunity, and cytokines IL-12 and IL-27 can modulate their phenotype and function. Tumour-specific CD8+ tumour-infiltrating lymphocytes (TILs) can be identified based on the surface expression of CD39, while CD8+ TILs that recognize cancer unrelated antigens do not. It is currently unclear how and why tumour-specific CD8+ T-cells uniquely express CD39. We hypothesize that IL-12 and IL-27 upregulate CD39 expression on CD8+ T-cells and improve effector activity of CD39+CD8+ T-cells, compared to their CD39- counterparts. Using in vitro stimulation assays, we identified that CD8+ T-cells upregulate CD39 in the presence of IL-12 and IL-27. Moreover, CD39+CD8+ T-cells produced higher levels of effector molecules, such as IFN-γ, than CD39- counterparts. Inhibiting IL-12 activity, in vivo, reduced CD39+CD8+ TIL frequency compared to controls, without changing the overall CD8+ TIL frequency. Our findings shed light on some underlying mechanisms of CD39 upregulation by CD8+ T-cells. |
