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Immunity Mar 2018Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor... (Review)
Review
Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor immunity by counteracting T cell-activating signals. Antibody-based PD-1-PD-L1 inhibitors can induce durable tumor remissions in patients with diverse advanced cancers, and thus expression of PD-L1 on tumor cells and other cells in the tumor microenviroment is of major clinical relevance. Here we review the roles of the PD-1-PD-L1 axis in cancer, focusing on recent findings on the mechanisms that regulate PD-L1 expression at the transcriptional, posttranscriptional, and protein level. We place this knowledge in the context of observations in the clinic and discuss how it may inform the design of more precise and effective cancer immune checkpoint therapies.
Topics: Animals; B7-H1 Antigen; Gene Expression Regulation; Humans; Immunotherapy; Lymphocyte Activation; Molecular Targeted Therapy; Neoplasms; Programmed Cell Death 1 Receptor; Signal Transduction; T-Lymphocytes
PubMed: 29562194
DOI: 10.1016/j.immuni.2018.03.014 -
Current Opinion in Immunology Jun 1997
Review
Topics: Animals; Humans; Immune System; Lymphocyte Activation; Signal Transduction
PubMed: 9203423
DOI: 10.1016/s0952-7915(97)80073-8 -
Cell Jan 1999
Review
Topics: Actins; Cytoskeleton; Lymphocyte Activation
PubMed: 9989492
DOI: 10.1016/s0092-8674(00)80954-x -
Current Opinion in Immunology Jun 2009
Topics: Animals; Cytotoxicity, Immunologic; Humans; Immunity, Cellular; Immunologic Memory; Lymphocyte Activation
PubMed: 19520560
DOI: 10.1016/j.coi.2009.05.020 -
Journal of Visualized Experiments : JoVE Jul 2020Traction force microscopy (TFM) enables the measurement of forces produced by a cell on a substrate. This technique infers traction force measurements from an...
Traction force microscopy (TFM) enables the measurement of forces produced by a cell on a substrate. This technique infers traction force measurements from an experimentally observed displacement field produced by a cell pulling on an elastic substrate. Here, we adapted TFM to investigate the spatial and temporal structure of the force field exerted by B cells when activated by antigen engagement of the B cell receptor. Gel rigidity, bead density, and protein functionalization must be optimized for the study of relatively small cells (~ 6 µm) that interact with, and respond specifically to ligands for cell surface receptors.
Topics: Humans; Lymphocyte Activation; Microscopy, Atomic Force
PubMed: 32773764
DOI: 10.3791/60947 -
Journal of Immunotoxicology Dec 2020Nonclinical immunotoxicity evaluation is an important component of safety assessment for pharmaceuticals. One assay that can be applied in a weight of evidence...
Nonclinical immunotoxicity evaluation is an important component of safety assessment for pharmaceuticals. One assay that can be applied in a weight of evidence assessment is the human lymphocyte activation (HuLA) assay, an antigen recall assay, similar in many respects to the T-cell-dependent antibody response (TDAR) in that cooperation of multiple immune cell types are needed to produce responses. This assay uses human cells and is more amenable than the TDAR to compound ranking and mechanistic studies. The HuLA assay requires less time and drug than TDAR assays, uses a relevant antigen (influenza), reflects a human immune response, and applies principles of the 3Rs to non-clinical safety assessment. Peripheral blood mononuclear cells (PBMC) from flu-immunized donors are re-stimulated with flu-vaccine in the presence of test articles, and proliferation is measured. Published data demonstrate the applicability of the HuLA assay, but it has not been evaluated for reproducibility across testing sites. To evaluate assay reproducibility, scientists from a consortium of institutions conducted the assay in parallel, using a common pool of donor PBMC, influenza vaccine, and known immunosuppressant compounds (cyclosporine A and mycophenolic acid). The HuLA assay was highly reproducible in identification of inhibition of antigen-specific responses, and there was significant agreement across testing sites in the half maximal inhibitory concentration (IC) values. Intra-site variability was the largest contributor to the variability observed within the assay. The HuLA assay was demonstrated to be ideally suited to comparing multiple compounds (i.e. compound ranking or benchmarking) within the same assay. Overall, the data reported herein support the HuLA assay as a useful tool in mechanistic evaluations of antigen-specific immune responses.
Topics: Biological Assay; Cells, Cultured; Cyclosporine; Cytotoxicity Tests, Immunologic; Drug Evaluation, Preclinical; Healthy Volunteers; Humans; Immunosuppressive Agents; Influenza Vaccines; Inhibitory Concentration 50; Leukocytes, Mononuclear; Lymphocyte Activation; Mycophenolic Acid; Reproducibility of Results
PubMed: 32124652
DOI: 10.1080/1547691X.2020.1725694 -
Journal of Controlled Release :... May 2018
Topics: Drug Implants; Female; Humans; Inflammation; Lymphocyte Activation; T-Lymphocytes; Vagina
PubMed: 29678269
DOI: 10.1016/j.jconrel.2018.04.008 -
Current Opinion in Immunology Apr 2016
Topics: Animals; Cell Differentiation; Humans; Lymphocyte Activation; Lymphocytes; Stem Cells
PubMed: 26923180
DOI: 10.1016/j.coi.2016.02.005 -
Molecular Immunology Dec 2015
Topics: Animals; Humans; Lymphocyte Activation; T-Lymphocytes
PubMed: 26552762
DOI: 10.1016/j.molimm.2015.10.006 -
Immunological Reviews May 2018Immunological memory, traditionally thought to belong to T and B cells, has now been extended to innate lymphocytes, including NK cells and ILC2s, myeloid cells such as... (Review)
Review
Immunological memory, traditionally thought to belong to T and B cells, has now been extended to innate lymphocytes, including NK cells and ILC2s, myeloid cells such as macrophages, also termed "trained immunity" and more recently to epithelial stem cells. In this review, we discuss the mechanisms underlying memory generation on ILC2s and speculate about their potential role in human allergic diseases, such as asthma. Moreover, we examine the relevance of the spontaneous ILC2 activation in the lung during the neonatal period in order to efficiently respond to stimuli later in life. These "training" of neonatal ILC2s may have an impact on the generation of memory ILC2s in the adulthood.
Topics: Age Factors; Animals; Asthma; Cell Differentiation; Humans; Immunity, Innate; Immunologic Memory; Lymphocyte Activation; Lymphocyte Subsets
PubMed: 29664572
DOI: 10.1111/imr.12643