Haematology 2018

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

• Upon interaction with ligands, PD-L1 and PD-L2, initiates an inhibitory signaling network that switches off activated T cells

T-reg

• 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

Shekhar S & Yang X. Cellular & Molecular Immunology 2012;9:380–5.