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Rationale for Targeting PD1/PD-L1 Pathway in Cancer
• PD1 expressed by Tregs, activated T cells (CD4 and CD8), activated B cells, NK cells
• PD-L1 is expressed by APCs and several cancers
T-reg
Shekhar S & Yang X. Cellular & Molecular Immunology 2012;9:380–5.
• Upon interaction with ligands,
PD-L1 and PD-L2, initiates an
inhibitory signaling network
that switches off activated T
cells
• Results in T cell exhaustion /
anergy - poor effector function
• Anti-PD1/PDL1 mAb led to
durable clinical responses in
NSCLC, RCC, Melanoma, HL
PD1 – programmed death 1; PDL – programmed death
ligand; NK – natural killer; APCs - antigen presenting cells