Abstract
Checkpoint programmed death-1 (PD-1)/programmed cell death ligands (PD-Ls) have been identified as negative immunoregulatory molecules that promote immune evasion of tumor cells. The interaction of PD-1 and PD-Ls inhibits the function of T cells and tumor-infiltrating lymphocytes (TIL) while increasing the function of immunosuppressive regulatory T cells (Tregs). This condition causes the tumor cells to evade immune response. Thus, 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. Furthermore, some monoclonal antibodies blockading PD-1/PD-Ls axis have achieved good effect and received Food and Drug Administration approval. The role of PD-1/PD-Ls in tumors has been well studied, but little is known on the mechanism by which PD-1 blocks T-cell activation. In this study, we provide a brief overview on the discovery and regulatory mechanism of PD-1 and PD-L1 dysregulation in tumors, as well as the function and signaling pathway of PD-1 and its ligands; their roles in tumor evasion and clinical treatment were also studied.
Highlights
Under normal physiological conditions, the major function of programmed death-1 (PD-1) is to inhibit effector T-cell activity and enhance the function and development of Tregs, which inhibit T-cell responses and prevent overstimulation of immune responses in peripheral tissues [1, 2]
PD-1 knockout (Pdcd1−/−) mice can lead to tissue sensitive to infection or late onset autoimmune disease with variable incidence depending on the background strain carrying the PD1 null animal [5,6,7]
Each of the novel NFAT/signal transducer and activator of transcription (STAT) elements interacts with the Pdcd1 promoter region and the chromatin structure of each regulatory region is altered in response to T-cell activation and cytokine stimulation in CD8 T cells, demonstrating that NFAT/STAT elements is associated with PD-1 expression [49, 54]
Summary
The major function of PD-1 is to inhibit effector T-cell activity and enhance the function and development of Tregs, which inhibit T-cell responses and prevent overstimulation of immune responses in peripheral tissues [1, 2]. JAK2 amplification promoted protein expression and activity, inducing PD-1 ligand transcription and enhancing sensitivity to JAK2 inhibition. Xiao et al identified that tumor-infiltrating T cells significantly upregulated the expression of the activator protein 1
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
