Figure 7.

Proposed mechanism by which JAK1 deficiency leads to cytotoxic T-cell resistance. Tumor-derived OT-I–MHC-I complex can activate OT-I T-cells to produce cytotoxic IFN-γ, TNF-α, granzyme, and perforin. IFN-γ can activate JAK–STAT signaling in tumor cells, leading to upregulation of multiple regulatory genes affecting T-cell activation and function. IFN-γ-induced MHC-I can sensitize tumor cells to T-cell-mediated killing, while IFN-γ-induced PD-L1 suppresses T-cell activation by interacting with PD-1 in T-cells.