Exploring the PD-L1 Pathway

Transcription

1 Active Within the tumor microenvironment Steps 1-3: Initiating and propagating anticancer immunity 1 may inhibit T-cell activity in the tumor microenvironment Dendritic cells capture cancer and then prime and activate s. Upregulation of can inhibit the last steps of the cancer immunity cycle by deactivating s in the tumor microenvironment. 1 Steps 4-5: Accessing the tumor is a potential biomarker 1 Activated s infiltrate the tumor microenvironment. for cancers As a result, tumor cells and Steps 6-7: -cell recognition and initiation of ity that overexpress 1 tumor-infi ltrating immune cells binds to T-cell receptors and Activated s in the, deactivating s. Once tumor microenvironment deactivated, s remain inhibited in release interferon gamma. s can recognize 2 overexpress and kill. target cancer cells, causing the release 2 the of tumor additional microenvironment. 1,2 Genentech is actively investigating cancer from as a the potential tumor. biomarker in oncology research and is committed 1 to pursuing the potential of personalized cancer immunotherapy for cancer patients. Exploring the Pathway expression has been detected on tumor cells and tumor-infi ltrating immune cells 1,9 Tumor 10 on tumor cells (stained brown below) may lead to the inhibition of activated s. 2 7 Tumor-infi ltrating immune cell 10 on tumor-infiltrating immune cells (stained brown below) may also lead to inhibition of activated s. 2,3 a new direction in cancer immunotherapy research WITHIN THE TUMOR MICROENVIRONMENT Tumor apoptosis 6 Tumor-infiltrating immune cells 5 Macrophage THE CANCER IMMUNITY CYCLE IN CANCER AS A POTENTIAL TARGET

2 2 Dendritic cell 3 WITHIN THE LYMPH NODE Active The cancer immunity cycle 4 WITHIN THE BLOOD VESSEL The cancer immunity cycle describes a natural process of how one s own immune system protects the body against cancer. 1 immunotherapy research seeks to understand how to utilize the body s adaptive immune defense against cancer s ability to evolve and evade destruction. 2 Steps 1-3: Initiating and propagating anticancer immunity 1 Dendritic cells capture cancer and then prime and activate s. Steps 4-5: Accessing the tumor 1 Activated s infiltrate the tumor microenvironment. 5 1 Steps 6-7: -cell recognition and initiation of ity 1 s can recognize and kill target cancer cells, causing the release of additional cancer from the tumor. 7 WITHIN THE TUMOR MICROENVIRONMENT Tumor apoptosis 6 THE CANCER IMMUNITY CYCLE

3 Programmed death-ligand 1 (): an inhibitory immune pathway exploited by cancer can evade the body s immune response. Many tumors and tumor-infi ltrating immune cells express high levels of. Under normal conditions, the pathway can play an important role in maintaining immune homeostasis. In cancer, the pathway can protect tumors from s by disrupting the cancer immunity cycle in two ways. 1-4 Within the lymph nodes may inhibit cancer immunity cycle propagation in the lymph nodes Overexpression of on tumor-infi ltrating immune cells can prevent the priming and activation of new s in the lymph nodes and subsequent recruitment to the tumor. 1-3 expression is upregulated on dendritic cells within the tumor microenvironment. 2,3 expressing dendritic cells travel from the tumor site to the lymph node. 5 binds to and receptors on s, suppressing activation. 3 Dendritic cell Within the tumor microenvironment may inhibit T-cell activity in the tumor microenvironment Upregulation of can inhibit the last steps of the cancer immunity cycle by deactivating s in the tumor microenvironment. 1 Activated s in the tumor microenvironment release interferon gamma. 2 As a result, tumor cells and tumor-infi ltrating immune cells overexpress. 2 binds to T-cell receptors and, deactivating s. Once deactivated, s remain inhibited in the tumor microenvironment. 1,2 IN CANCER

4 The pathway is a potential target in cancer research Data suggest that may be one of the primary immunosuppressive drivers in multiple types of cancer. Inhibiting interactions may prevent T-cell suppression throughout the tumor microenvironment. 2,3 Epithelial cell Active Macrophage TCR PD-L2 MHC interference affects and binding 2,3 Preventing from binding to its receptors on s may release the s from the inhibitory effect of 2 Preclinical studies suggest that preventing both interactions may propagate T-cell activity 2 PD-L2 interactions should not be affected by interference 2,6 As suggested by preclinical studies, PD-L2 is another ligand primarily expressed on normal tissues and immune cells, protecting them during an immune response to maintain immune homeostasis 2,6 8 and PD-L2 can both bind to, which may lead to T-cell deactivation 2 Preclinical studies suggest that interfering with activity does not inhibit PD-L2/ interactions 2,6 is a potential biomarker for cancers that overexpress Genentech is actively investigating as a potential biomarker in oncology research and is committed to pursuing the potential of personalized cancer immunotherapy for cancer patients. expression has been detected on tumor cells and tumor-infi ltrating immune cells 1,9 Tumor 10 on tumor cells (stained brown below) may lead to the inhibition of activated s. 2 Tumor-infi ltrating immune cell 10 on tumor-infiltrating immune cells (stained brown below) may also lead to inhibition of activated s. 2,3 Tumor-infiltrating immune cells AS A POTENTIAL TARGET

5 Programmed death-ligand 1 (): an inhibitory immune pathway exploited by cancer is an inhibitory ligand expressed by tumors and tumor-infiltrating immune cells in many cancers 2,4 is a potential biomarker for cancers that overexpress 2 binding to either or receptors inhibits s 2,3 Discover the pathway, a focus of investigation and cancer immunotherapy research, by visiting Discover.ResearchPDL1.com References: 1. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39: Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy inhibiting programmed death-ligand 1 and programmed death-1. Clin Res. 2012;18: Keir ME, Butte MJ, Freeman GJ, Sharpe AH. and its ligand in tolerance and immunity. Annu Rev Immunol. 2008;26: Quezada SA, Peggs KS. Exploiting CTLA-4, and to reactivate the host immune response against cancer. Br J. 2013;108: Motz GT, Coukos G. Deciphering and reversing tumor immune suppression. Immunity. 2013;39: Topalian SL, Drake CG, Pardoll DM. Targeting the /B7-H1() pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24: Rozali EN, Hato SV, Robinson BW, Lake RA, Lesterhuis WJ. Programmed death ligand 2 in cancer-induced immune suppression. Clin Dev Immunol. 2012;2012: Latchman Y, Wood CR, Chernova T. PD-L2 is a second ligand for and inhibits activation. Nat Immunol. 2001;2: Sznol M, Chen L. Antagonist antibodies to and B7-H1 () in the treatment of advanced human cancer. Clin Res. 2013;19: Data on file. Genentech, Inc Genentech USA, Inc. All rights reserved. PDL/010915/0002(1) Printed in USA.