Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
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.

PubMed Disclaimer

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

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

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

Publication types