PD-1 and its ligands in tolerance and immunity.

@article{Keir2008PD1AI,
  title={PD-1 and its ligands in tolerance and immunity.},
  author={Mary E. Keir and Manish J. Butte and Gordon J. Freeman and Arlene H. Sharpe},
  journal={Annual review of immunology},
  year={2008},
  volume={26},
  pages={
          677-704
        }
}
Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. Immune responses to foreign and self-antigens require specific and balanced responses to clear pathogens and tumors and yet maintain tolerance. Induction and maintenance of T cell tolerance requires PD-1, and its ligand PD-L1 on nonhematopoietic cells can limit effector T cell responses and protect tissues from immune… 

Figures and Tables from this paper

Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond.

Clinically, antibodies targeting PD-1/PD-L1 reinvigorate the "exhausted" T cells in TME and show remarkable objective response and durable remission with acceptable toxicity profile in large numbers of tumors such as melanoma, lymphoma, and mismatch-repair deficient tumors.

PD-1 and its ligands are important immune checkpoints in cancer

The blockade of PD-1/PD-L1 enhances anti-tumor immunity by reducing the number and/or the suppressive activity of Tregs and by restoring the activity of effector T cells.

Biochemical Signaling of PD-1 on T Cells and Its Functional Implications

A brief overview of the signaling events that are regulated by PD-1 triggering are provided, and their implications on cell intrinsic and extrinsic mechanisms that determine the fate and function of T effector cells are discussed.

The Programmed Death-1 Immune-Suppressive Pathway: Barrier to Antitumor Immunity

The mechanisms by which PD-L1 impairs antitumor immunity are reviewed and established and experimental strategies for maintaining T cell activation in the presence of PD- L1–expressing cells in the tumor microenvironment are discussed.

PD-L1

The immunobiology of PD-L1 is discussed, with a particular focus on its clinical significance in malignancy, by inducing durable tumour regression in numerous malignancies including metastatic lung cancer, melanoma and many others.

Regulation of PD-1/PD-L1 pathway and resistance to PD-1/PD-L1 blockade

The possibility of combined epigenetic therapy with PD-1 blockade as a potential promising approach for cancer treatment and strategies to increase the efficacy of immunotherapy are discussed.

Role of the PD-1 Pathway in the Immune Response

The upregulation of PD-L1 on nonhematopoietic cells of the allograft may actively participate in the inhibition of immune responses and provide tissue-specific protection in transplantation.

A snapshot of the PD-1/PD-L1 pathway

A snapshot of the PD-1/PD-L1 molecular structure, mechanisms controlling their expression, signaling modulated by PD-2, current anti-PD-1 or anti- PD- L1 therapies, and the future perspectives to overcome the resistance is provided.

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

The PD-1:PD-L1/L2 pathway also mediates potent inhibitory signals to hinder the proliferation and function of T effector cells and have inimical effects on antiviral and antitumor immunity.
...

References

SHOWING 1-10 OF 157 REFERENCES

Tissue expression of PD-L1 mediates peripheral T cell tolerance

Evidence is provided that PD-L 1 expression on parenchymal cells rather than hematopoietic cells protects against autoimmune diabetes and point to a novel role for PD-1–PD-L1 interactions in mediating tissue tolerance.

Programmed Death-1 Targeting Can Promote Allograft Survival1

Data show that when combined with limited immunosuppression, or in the context of submaximal TCR or costimulatory signals, targeting of PD-1 can block allograft rejection and modulate T and B cell-dependent pathologic immune responses in vivo.

PD-L2 is a second ligand for PD-1 and inhibits T cell activation

These studies show overlapping functions of PD-L1 andPD-L2 and indicate a key role for the PD- L–PD-1 pathway in regulating T cell responses.

Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation

It is reported here that the ligand of PD-1 (PD-L1), an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells, is a member of the B7 gene family.

Blockade of Programmed Death-1 Ligands on Dendritic Cells Enhances T Cell Activation and Cytokine Production 1

It is shown that blockade of PD-L2 on dendritic cells results in enhanced T cell proliferation and cytokine production, including that of IFN-γ and IL-10, which is consistent with the hypothesis that iDC have a balance of stimulatory vs inhibitory molecules that favors inhibition.

PD-1 and PD-1 ligands: from discovery to clinical application.

The history ofPD-1 research since its discovery and recent findings that suggest promising future for the clinical application of PD-1 agonists and antagonists to various human diseases are summarized.

Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade

The results suggest that the expression of PD-L1 can serve as a potent mechanism for potentially immunogenic tumors to escape from host immune responses and that blockade of interaction between PD-1 andPD-L may provide a promising strategy for specific tumor immunotherapy.

Endothelial Programmed Death-1 Ligand 1 (PD-L1) Regulates CD8+ T-Cell–Mediated Injury in the Heart

Myocardial PD-L1, mainly localized on endothelium, is critical for control of immune-mediated cardiac injury and polymorphonuclear leukocyte inflammation.

Involvement of the Programmed Death-1/Programmed Death-1 Ligand Pathway in CD4+CD25+ Regulatory T-Cell Activity to Suppress Alloimmune Responses

The blockade of the PD-1/PD-L1 pathway abrogates Treg-mediated immunoregulation, thus suggesting that thePD-1 /PD- L1 pathway is required for Treg suppression of the alloreactive responses of CD4+CD25-T cells.
...