DISSECTION OF T CELL ACTIVATION PHASES FOR CHECK POINT BLOCKADE IMMUNOTHERAPY

Checkpoint blockade immunotherapy relies on the restoration of effector responses in precursor-exhausted T cells. Nevertheless, many inhibitory receptors are upregulated soon after activation and reach high levels at phases. In addition to functional status type 1 helper (Th1) cells, timing duration PD-1 CTLA-4 considered as critical factors for retaining cell responsiveness. Here, we used a previously established ex-vivo model display decline Th1 determine state-of-function which may critically modulate success checkpoint blockade. absence and/or blockade, proliferation IFN-γ, TNF-α, IL-2 secretion capacities cells were gradually abolished stimulation was continued. When applied an early stage, extension period interfered with upregulation multiple (PD-1, LAG3, TIM-3, CTLA-4) restricted hyporesponsiveness. The that already expressed prior also downregulated potentially through endocytic pathway. A time point representing late stages responses, preceded exhaustion, determined therapeutic window short-term check conclusion, inhibitor therapy not only adjust reactivation hyporesponsive but can restrict induction de novo exhaustion.