Figure 3.

PD-L1-dependent and independent resistance by CD8 effector cells and tumor cells. Tumor cells secrete IFN-y and IFN-I that can bind to IFNGR and IFNAR on tumor cells and promote PD-L1-independent resistance through constitutive activation of STAT1. Tumor cells and CD8 effector cells produce and secrete IFN-y that increases PD-L1 in the TME and causes exhaustion of CD8 cells promoting PD-L1-dependent resistance. CD8 effector cells increase production of CCL22, a chemoattractant that binds to CCR4 on Tregs increasing their presence in the TME, thus decreasing CD8 effector cell activity.