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E-914 Copyright © 2015 Abcam, All rights reserved. RabMAb ® is a registered trademark of Abcam. *Adapted from Pardoll, et al., 2012 Discover more at abcam.com/cancer Cancer immunotherapy - Immune checkpoint T cell proliferation T cell activation T cell priming Tumor infiltration Antigen capture Dendritic cell Activated T cell Activated T cell Naive T cell Tumor cell Antigens Tumor apoptosis T cell activation by dendritic cell Dendritic cell Activated T cell Antigen TCR CD28 CD80/86 T cell inhibition by tumor cell PDL1 PD1 Tumor cell - Growing Inhibited T cell T cell activation by immunotherapy Activated T cell Tumor cell - Dying Activated T cell Tumor cell Tumor cell death T cell inhibition by dendritic cell Dendritic cell Inhibited T cell PDL1 PD1 Antigen Presenting Cell T Cell T Cell Regulation PD-L1 PD-1 Inhibition PD-L2 PD-1 n/a CD80 / CD86 CD28 Activation CD80 / CD86 CTLA4 Inhibition B7RP1 (ICOSL) ICOS Activation B7-H3 (CD276) n/a Inhibition B7-H4 (VTCN1) n/a Inhibition B7-H5 CD28H Activation n/a VISTA Inhibition HVEM BTLA Inhibition CD40 CD40L Activation OX40L OX40 Activation CD137L CD137 Activation CD70 CD27 Activation GAL9 TIM3 Inhibition GITRL GITR Activation MHC-II LAG-3 Inhibition Cancer immunity cycle T cell activation is regulated by stimulatory and inhibitory signals that fine-tune the response and maintain the balance between appropriate recognition and destruction of tumors and inappropriate overstimulation of immune responses. Please see the table for a list of targets that regulate T cell activation. T cell is inhibited when: Co-inhibitors of T cell are bound to their receptors on APC. Through these interactions the immune system is regulated to minimize autoimmune inflammation. Regulators of T cell activation* Blocking PD-L1 with a monoclonal antibody interferes with T cell inhibition and active immune response leads to tumor cell death. T cell is activated when: T-cell receptor recognizes an antigen on the surface of the antigen presenting cell (APC). Co-stimulatory interaction occurs between T cell and APC. Cancer immunotherapy strategies involve blocking of key immune checkpoint inhibitors to ensure immune responses remain effective against cancer. Immunotherapies against PD-L1 and PD-1 reveal promising results against some cancer types. PD-1/PD-L1 interaction reduces cytokine production and suppresses T cell proliferation. Tumor cells exploit this immune checkpoint pathway as a mechanism to evade detection and inhibit the immune response. This leads to cancer progression. PD-L1 [28-8] RabMAb ® knockout validated antibody Key features Knockout (KO) cell line validated in key applications: IHC, FC, WB Highly specific for human PD-L1; no cross-reactivity with human PD-L2 Tested with pathologically validated positive and negative controls Generated using extracellular domain of PD-L1 protein – observed membrane specific staining Extensive validation in automated protocols (Phillips et al., 2015) Reference Phillips, T., Simmons, P., Inzunza, H., Cogswell, J., Novotny, J., Taylor, C. and Zhang, X. (2015). Development of an Automated PD-L1 Immunohistochemistry (IHC) Assay for Non–Small Cell Lung Cancer. Applied Immunohistochemistry & Molecular Morphology, 23(8), pp.541-549. B-CAP Cells - High HCC70 Cells - Medium ES-2 Cells - Low COLO205 Cells - None (Cancer cell lines with varying levels of PD-L1 expression) Wild Type L2987 Cells PD-L1 KO L2987 Cells
