UNASSIGNED: @entity25909 - and @entity31175 -primed @entity405 T cells mount powerful effector responses upon recall, but even without recall these dual-costimulated T cells respond to signal 3 cytokines such as IL-12. We searched for alternative signal 3 receptor pathways and found the @entity1192 family member @entity34694 . Although IL-36 alone did not stimulate effector @entity405 T cells, in combination with IL-12, or more surprisingly @entity1199 , it induced striking and rapid TCR-independent @entity379 synthesis. To understand how signal 3 responses functioned in dual-costimulated T cells we showed that @entity1199 induced @entity34694 gene expression in a JAK/STAT-dependent manner. These data help delineate a sequential stimulation process where @entity1199 conditioning must precede IL-36 for @entity379 synthesis. Importantly, this responsive state was transient and functioned only in effector T cells capable of aerobic glycolysis. Specifically, as the effector T cells metabolized @entity413 and consumed @entity3612 , they also retained potential to respond through @entity34694 . This suggests that T cells use innate receptor pathways such as the @entity34694 /axis when programmed for aerobic glycolysis. To explore a function for @entity34694 in vivo, we showed that dual costimulation therapy reduced B16 @entity320 growth while increasing @entity34694 gene expression. In summary, cytokine therapy to eliminate @entity5 may target effector T cells, even outside of @entity20432 specificity, as long as the effectors are in the correct metabolic state.

Costimulation Endows Immunotherapeutic XXXX T Cells with IL-36 Responsiveness during Aerobic Glycolysis.

@entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma tumor'] @entity25909 :: ('7293', 'Gene') :: ['CD134'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumors'] @entity31175 :: ('3604', 'Gene') :: ['CD137'] @entity34694 :: ('8808', 'Gene') :: ['IL-36R'] @entity1192 :: ('3552', 'Gene') :: ['IL-1'] @entity379 :: ('3458', 'Gene') :: ['IFN-y'] @entity3612 :: ('D013481', 'Chemical') :: ['O2'] @entity20432 :: ('C007145', 'Chemical') :: ['TCR'] @entity1199 :: ('3558', 'Gene') :: ['IL-2'] @entity405 :: ('925', 'Gene') :: ['CD8'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity405 :: (925,Gene) :: ['CD8']
