Reducing CD73 Expression by IL1β-Programmed Th17 Cells Improves Immunotherapeutic Control of Tumors

摘要: T helper (Th)-17 subsets hold promise in adoptive cell transfer therapy for cancer. However, ex vivo programming of Th17 cells presence TGF-β increases surface expression ectonucleotidases CD39 and CD73, that turn susceptibility to immunosuppression reduces effector functions. Our data shows ATP mediated suppression IFN-γ production by can be overcome either genetic ablation CD73 or generating independent IL-1β. cultured IL-1β are also highly polyfunctional, express high level molecules exhibit better short-term control B16-F10 murine melanoma, despite reduced stem like properties. Adding at low dose does not up regulate expression, but induces stemness, drastically improves anti-tumor function cells. It is likely property dependent due their glycolytic capacity, since pyruvate containing media impaired glycolysis its potential. Thus, our suggests induction ectonucleotidase TGF-β, culture conditions need reconsidered exploiting full potential therapy.