The impact of PD-1 blockade on T-cell dynamics is determined by the context, including integration of other costimulatory signals. Potential autoimmune toxicity of anti-PD-1 may be offset by the enhancement of Treg function due to blockade of PD-1 on Tregs.
Antibodies can also have agonistic effects, particularly if Fc-binding is intact, leading to additional parameters. Further study of the immunological synapse in the TME is needed to appreciate other interactions within and between SMACs to achieve optimal results for immunotherapy. I thank members of my lab for stimulating discussions and many insights.
National Center for Biotechnology Information , U. Cancer Immunol Res. Author manuscript; available in PMC Dec Michael L. Author information Copyright and License information Disclaimer. Copyright notice. The publisher's final edited version of this article is available free at Cancer Immunol Res.
See other articles in PMC that cite the published article. Abstract The molecular interactions underlying regulation of the immune response take place in a nano-scale gap between T cells and antigen presenting cells, termed the immunological synapse. Introduction T cell dependent immune responses protect the host from cancer 1 , 2 , but also participate in destructive autoimmunity 3 , 4.
Open in a separate window. Figure 1. T-cell antigen receptor TCR interaction with MHC-peptide complexes controls the specificity of the immune response and the source of antigens in both cellular and humoral responses. Figure 2. Adhesion receptors Adhesion molecules are critical for sensitive antigen recognition required for tumor rejection Costimulation Costimulatory receptors have minimal signaling or adhesive activity on their own, but can enhance adhesion and signaling locally when combined with other stimuli, primarily through the TCR 63 , Checkpoint blockade Co-inhibitory or checkpoint receptors are a natural complement to the costimulators - they use various negative signaling pathways, often recruiting tyrosine phosphatases, such as SHP1 and SHP2, to attenuate tyrosine kinase cascades or other signaling pathways.
Directed secretion: a synaptic advantage? Conclusions The immunological synapse mode of stable engagement of targets benefits the attack on the tumor. Acknowledgements I thank members of my lab for stimulating discussions and many insights. References 1. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug.
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What Counts in the Immunological Synapse? Publication Type. More Filters. Impact of the immunological synapse on T cell signaling. Results and problems in cell differentiation.
T cell activation requires interactions of T cell antigen receptors and peptides presented by major histocompatibility complex molecules in an adhesive junction between the T cell and … Expand. View 2 excerpts, cites background. Continuous T cell receptor signaling required for synapse maintenance and full effector potential. Nature Immunology. A dynamic view of the immunological synapse. Seminars in immunology. T cell activation requires interactions of T cell antigen receptors TCR and peptides presented by major histocompatibility complex molecules MHCp in an adhesive junction between the T cell and … Expand.
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The immunological synapse provides a platform for such communication by coupling activated lymphocytes … Expand. Information transfer at the immunological synapse. Current Biology. The immunological synapse: required for T cell receptor signalling or directing T cell effector function?
The duration of antigenic stimulation determines the fate of naive and effector T cells.
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