SLIDE 12 CTLA-4 vs PD1: checkpoint inhibitors CTLA-4 vs PD1: checkpoint inhibitors
CTLA-4 PD1
Migrates from intracellular stores to T cell : APC synapse upon T-cell activation1 Expressed on cell surface or induced by T cell interaction; redistributes to T cell : APC synapse on T-cell activation1 Inhibits Akt but not PI3K activity1 Inhibits PI3K and downstream Akt1 Dual ligands (B7.1; B7.2)2 Dual ligands (PD-L1; PD-L2)2 E d ti t d T ll
1 2
E d f i ll Expressed on activated T cells1,2 Expressed on a range of immune cells, including T cells Ligands broadly expressed on APCs / tiss es thro gho t the bod
1 2
Ligands expressed on tumours and imm ne cells and to a lesser e tent tissues throughout the body1,2 immune cells and, to a lesser extent, normal tissues2 Activation through association of APC and T cell in periphery followed by Activation through association of tumour and T cell at tumour site and APC and and T cell in periphery followed by distribution of activated T cells to tumor sites3 and T cell at tumour site and APC and T cell in lymph nodes3
K i ME A R I l 2008 26 677 704
12
Mercury: 1506HQ13NP08597 -01-IT Approved Oct 2013; Expires Oct 2015
Keir ME. Annu Rev Immunol 2008;26:677–704. Korman AJ, et al. Adv Immunol 2006;90:297–339. Parry RV, et al. Mol Cell Biol 2005;25:9543–9553.
