Figure 7.

Schematic representation of pathways leading to cytotoxic lymphocyte killing upon IAP or PD-1 antagonism. Ligation of TCR with cognate tumor antigen or NK cell activating receptor stimulation drives TNF production. PD-L1 expression on tumor cells, dampens signaling cascades that drive TNF production and perforin/granzyme-mediated apoptosis. Furthermore, tumor cell expression of cIAP1/2 protects them from apoptosis mediated by TNF released from CLs. Thus co-inhibition of PD-L1 and IAPs increases TNF production from CLs, and decreases the TNF threshold for apoptosis induction