Fig. 2

Mechanism of the PD pathway in driving tumor-associated immune evasion. Tumor cells, tumor-associated antigen-presenting cells (APCs), and stromal cells upregulate PD-L1 in response to ongoing immune responses, mainly through the action of IFN-γ. The ligation of PD-1 by PD-L1 delivers inhibitory signals to T cells, leading to T cell anergy, functional exhaustion, and apoptosis. PD-1-PD-L1 interaction also favors conversion of T cells to the regulatory T cell (Treg) phenotype with secretion of inhibitory cytokines, such as IL-10. PD-1 on myeloid cells also impairs dendritic cell functions. In addition, PD-L1 reversed signaling on tumor cells can serve as a “Molecular Shield” protecting tumor cells from CTL-mediated killing. IFN-γR: IFN-γ receptor