Although PD-1 and its ligands (PD-L1 and PD-L2) are stimulating molecules of the immune-checkpoint pathway, with primary function to limit inflammatory response and autoimmunity, tumor cells have found a way to exploit these molecules by obtaining the opportunity to respond with PD-L1 expression in cytokine signals and thus to evade immune surveillance.
Accordingly, peptide/calcitriol liposomes leverage DC PD-L1 for antigen-specific T cell regulation and induce antigen-specific tolerance in inflammatory autoimmune diseases.
Moreover, this TME regulation strategy can effectively improve the antitumor effect of anti-PDL1 therapy without the employment of any immune agonists to avoid the autoimmunity.
In addition, the development of multifarious autoimmune diseases as immune-related adverse events of anti-CTLA-4 and anti-PD-1/PD-L1 therapies and the successful clinical application of the CD28 blocking therapy using CTLA-4-Ig to the treatment of arthritis assure their crucial roles in the regulation of autoimmunity in human.
Monoclonal antibodies (mAbs) targeting immune checkpoints, such as mAbs anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed cell death protein-1/programmed cell death ligand-1 (anti-PD-1/PD-L1), have revolutionized the treatment of many malignancies, but they induce thyroid dysfunction in up to 10% of patients, presumably by enhancing autoimmunity.
The programmed death 1 receptor (PD-1) and its ligand programmed death ligand-1 (PD-L1) are important negative regulators of immune activity, preventing destruction of normal tissues and autoimmunity.
Our findings indicate that Klf1 and Egr2 are modulators of PD-L1-mediated immune suppression in CD4<sup>+</sup> T cells and might provide new insights into therapeutic targets for autoimmune diseases and malignancies.
The interaction of programmed cell death-1 and its ligand-1 (PD-L1) serves as a regulatory check against excessive immune response to antigen and autoimmunity.
Under physiological conditions, the PD-1/PD-L1 interaction is essential in the development of immune tolerance preventing excessive immune cell activity that can lead to tissue destruction and autoimmunity.
The programmed cell death 1 receptor (PD-1) and its ligand (PD-L1) are important negative regulators of immune activity, preventing the destruction of normal tissues and autoimmunity.
Programmed death-1 (PD-1)/PD-L1 immunotherapy has shown evidence of durable responses in certain malignancies such as melanoma, lung cancer, and renal cell carcinoma.PD-L1 positive tumors promote autoimmunity against the tumor; therefore, PD-1/PD-L1 blockade may be beneficial.Molecular profiling could possibly result in improved targeted therapy for certain malignancies.
Together, we propose the existence of a novel B7-H1-mediated immune-regulatory pathway in T cells, which selectively limits murine and human TH17 cell responses and might be therapeutically exploited to control TH17-mediated autoimmunity.