Cited by 614Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

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The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation

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Bardhan, Kankana, Anagnostou, Theodora, Boussiotis, Vassiliki A.·2016·Frontiers in Immunology

DOI 10.3389/fimmu.2016.00550PMC PMC5149523

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Abstract

The immune system has the difficult challenge of discerning and defending against a diversity of microbial pathogens, while simultaneously avoiding self-reactivity. T lymphocytes function as effectors and regulators of the immune system. While central tolerance mechanism results in deletion of the majority of self-reactive T lymphocytes during thymic selection, a fraction of self reactive lymphocytes escapes to the periphery and retains the potential to inflict destructive autoimmune pathology. The immune system evolved various mechanisms to restrain such auto-reactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs). These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programmed cell death 1 (PD-1) receptor (CD279) and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC; CD273) plays a vital role in the induction and maintenance of peripheral tolerance and for the maintenance of T cell homeostasis. In contrast to its beneficial role in self-tolerance, the PD-1: PD-L1/L2 pathway mediates potent inhibitory signals that prevent the expansion and function of T effector cells and have detrimental effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events that are regulated by PD-1 triggering, and their consequences on the function of T effector cells.

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Carter, 2002, PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2, Eur J Immunol, 32, 634, 10.1002/1521-4141(200203)32:3634::AID-IMMU6343.0.CO;2-9 · DOI

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Authors: Bardhan, K., Anagnostou, T., & Boussiotis, V. A.
Affiliations: Beth Israel Deaconess Medical Center (US)
Mayo Clinic (US)
Corresponding author: Boussiotis, Vassiliki A.
ORCID: Bardhan, Kankana
Anagnostou, Theodora
Boussiotis, Vassiliki A.
Venue: Frontiers in Immunology
Publisher: Frontiers Media SA
Published: 2016-12-12
Volume: 7
Pages: 550-550
ISSN: 1664-3224 (ISSN-L)
DOI: 10.3389/fimmu.2016.00550
PMC: PMC5149523
OpenAlex: W2560827811
Cited by: 606
References: 210
Citations by year: 2026: 38 · 2025: 53 · 2024: 83 · 2023: 60 · 2022: 63 · 2021: 100 · 2020: 69 · 2019: 74 · 2018: 45 · 2017: 20
FWCI: 4.66
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Immunology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Foundation for the National Institutes of Health (CA183605, CA183605S1, AI098129-01)
U.S. Department of Defense (PC140571)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: PD-1, PD-L1, PD-L2, immune checkpoint, T cell tolerance, peripheral tolerance, T cell homeostasis, T cell anergy, regulatory T cells, antitumor immunity, antiviral immunity, immune checkpoint blockade, T cell signaling

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The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation

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