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Review
. 2012 Apr;24(2):207-12.
doi: 10.1016/j.coi.2011.12.009. Epub 2012 Jan 9.

Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity

Suzanne L Topalian  1 , Charles G Drake, Drew M Pardoll
Affiliations
Review

Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity

Suzanne L Topalian et al. Curr Opin Immunol. 2012 Apr.

Abstract

Genetic alterations and epigenetic dysregulation in cancer cells create a vast array of neoepitopes potentially recognizable by the immune system. Immune checkpoint blockade has the capacity to enhance and sustain endogenous immunity against non-mutated tumor-associated antigens as well as uniquely mutant antigens, establishing durable tumor control. Recent evidence from preclinical models highlights the pivotal role of the Programmed Death-1 (PD-1) T cell co-receptor and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, in maintaining an immunosuppressive tumor microenvironment. Encouraging early clinical results using blocking agents against components of the PD-1 pathway have validated its importance as a target for cancer immunotherapy.

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Figures

Figure 1
Figure 1
PD-1 and CTLA-4 play distinct roles in regulating T cell immunity. CTLA-4 modulates the early phases of activation of naïve or memory T cells in response to TCR stimulation by MHC-peptide complexes displayed by antigen presenting cells (“signal 1”). In contrast, PD-1 is expressed on antigen-experienced T cells in the periphery, and serves to limit the activity of T cells at the time of an inflammatory response, thereby protecting normal tissues from collateral destruction. DC, dendritic cell.
Figure 2
Figure 2
Anti-PD-1 and anti-B7-H1/PD-L1 antibodies (mAbs) might behave differently owing to their ability to block distinct sets of inhibitory interactions. Anti-PD-1 mAbs can block its binding to both B7-H1/PD-L1 and B7-DC/PD-L2, abrogating an inhibitory PD-1-mediated signal in T cells; however, the inhibitory interaction of B7-H1/PD-L1 with B7.1 on T cells is not affected. Conversely, anti-B7-H1/PD-L1 mAbs can block its interactions with both B7.1 and PD-1, but will not block the inhibitory interaction of B7-DC/PD-L2 with PD-1. Both anti-PD-1 and anti-B7-H1/PD-L1 mAbs could potentially block transmission of a retrograde pro-survival signal through B7-H1/PD-L1 into tumor cells [43]. APC, antigen presenting cell.
See this image and copyright information in PMC

References

    1. Topalian SL, Weiner G, Pardoll DM. Cancer immunotherapy comes of age. J Clin Oncol. 2011 - PMC - PubMed
    1. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515–548. - PubMed

    1. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11:3887–3895. This seminal report describes the cloning of PD-1 (named for programmed death-1) from T cells undergoing activation induced cell death. Later studies demonstrated that PD-1 inhibits immunity through mechanisms other than apoptosis induction.

    1. Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol. 2007;19:813–824. - PubMed
    1. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704. - PMC - PubMed

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