Developments in anticancer vaccination: budding new adjuvants

2020 ◽  
Vol 401 (4) ◽  
pp. 435-446 ◽  
Author(s):  
Sandra Santos-Sierra
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Escape ◽  
Adaptive Immune System ◽  
Cell Detection ◽  
Cancer Vaccination ◽  
Tlr Agonists ◽  
Adaptive Immune ◽  
Anti Cancer ◽  
The Right

AbstractThe immune system has a limited capacity to recognize and fight cells that become cancerous and in cancer patients, the immune system has to seek the right balance between cancer rejection and host-immunosupression. The tumor milieu builds a protective shell and tumor cells rapidly accumulate mutations that promote antigen variability and immune-escape. Therapeutic vaccination of cancer is a promising strategy the success of which depends on a powerful activation of the cells of the adaptive immune system specific for tumor-cell detection and killing (e.g. CD4+ and CD8+ T-cells). In the last decades, the search for novel adjuvants that enhance dendritic cell (DC) function and their ability to prime T-cells has flourished and some Toll-like receptor (TLR) agonists have long been known to be valid immune adjuvants. The implementation of TLR-synthetic agonists in clinical studies of cancer vaccination is replacing the initial use of microbial-derived products with some encouraging results. The purpose of this review is to summarize the latest discoveries of TLR-synthetic agonists with adjuvant potential in anti-cancer vaccination.

scholarly journals T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

scholarly journals Role of T Lymphocytes in Type 2 Diabetes and Diabetes-Associated Inflammation

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Chang Xia ◽  
Xiaoquan Rao ◽  
Jixin Zhong
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
T Cells ◽  
Immune System ◽  
Critical Role ◽  
Adaptive Immune System ◽  
Metabolic Inflammation ◽  
Adaptive Immune

Although a critical role of adaptive immune system has been confirmed in driving local and systemic inflammation in type 2 diabetes and promoting insulin resistance, the underlying mechanism is not completely understood. Inflammatory regulation has been focused on innate immunity especially macrophage for a long time, while increasing evidence suggests T cells are crucial for the development of metabolic inflammation and insulin resistance since 2009. There was growing evidence supporting the critical implication of T cells in the pathogenesis of type 2 diabetes. We will discuss the available effect of T cells subsets in adaptive immune system associated with the procession of T2DM, which may unveil several potential strategies that could provide successful therapies in the future.

scholarly journals Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1750-1758 ◽  
Author(s):  
James L. Wynn ◽  
Philip O. Scumpia ◽  
Robert D. Winfield ◽  
Matthew J. Delano ◽  
Kindra Kelly-Scumpia ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Adaptive Immune System ◽  
Neutrophil Recruitment ◽  
Polymicrobial Sepsis ◽  
Type I ◽  
Sepsis Mortality ◽  
Tlr Agonists ◽  
Adaptive Immune ◽  
Increased Risk

Abstract Neonates exhibit an increased risk of sepsis mortality compared with adults. We show that in contrast to adults, survival from polymicrobial sepsis in murine neonates does not depend on an intact adaptive immune system and is not improved by T cell–directed adaptive immunotherapy. Furthermore, neonates manifest an attenuated inflammatory and innate response to sepsis, and have functional defects in their peritoneal CD11b+ cells. Activation of innate immunity with either a Toll-like receptor 4 (TLR4) or TLR7/8 agonist, but not a TLR3 agonist, increased the magnitude, but abbreviated the early systemic inflammatory response, reduced bacteremia, and improved survival to polymicrobial sepsis. TLR4 agonist pretreatment enhanced peritoneal neutrophil recruitment with increased oxidative burst production, whereas the TLR7/8 agonist also enhanced peritoneal neutrophil recruitment with increased phagocytic ability. These benefits were independent of the adaptive immune system and type I interferon signaling. Improving innate immune function with select TLR agonists may be a useful strategy to prevent neonatal sepsis mortality.

scholarly journals T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

2020 ◽  
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

AbstractBackground: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α-synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective: To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

scholarly journals Persistent SARS-CoV-2 presence is companied with defects in adaptive immune system in non-severe COVID-19 patients

2020 ◽  
Author(s):  
Bing Liu ◽  
Junyan Han ◽  
Xiaohuan Cheng ◽  
Long Yu ◽  
Li Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Immune Cells ◽  
Healthy Subjects ◽  
Laboratory Data ◽  
Adaptive Immune System ◽  
Lymphocyte Subpopulations ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

AbstractBackgroundCOVID-19 has been widely spreading. We aim to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding.Methods37 non-severe patients with persistent SARS-CoV-2 presence transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to PP (persistently positive) group, which was further allocated to PPP group (n=19) and PPN group (n=18), according to their testing results after 7 days (N=negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n=37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison.ResultsCompared with PA patients, PP patients had much improved laboratory findings, including WBCs, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, albumin, AST, CRP, SAA, and IL-6. The absolute numbers of CD3+ T cells, CD4+ T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative.ConclusionPersistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients.SummaryDefects in adaptive immune system, including reduced T cells and B cells, were frequently observed in non-severe COVID-19 patients with persistent SARS-CoV-2 shedding. Assessment of immune system could be clinically relevant for discharge management.

3. Adaptive immunity: a voyage of (non-)self-discovery

2017 ◽  
pp. 30-41
Author(s):  
Paul Klenerman
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Lymphocytes ◽  
Adaptive Immunity ◽  
Single Unit ◽  
Adaptive Immune System ◽  
Adaptive Immune ◽  
System A ◽  
Self Discovery ◽  
B And T Lymphocytes

How does the immune system respond to such diverse threats, including viruses never encountered previously by us as a species? The inherent diversity in the immune system can be explained by examining how the adaptive immune system is built, in particular the receptors on B and T lymphocytes. ‘The adaptive immune system: a voyage of (non-)self-discovery’ describes B and T cells, receptors, and the creation of antibodies. Antibody genes are not created as a single unit but are made up from smaller parts, generating many more possible combinations. The antibodies that are created from the genetic template are further honed, becoming highly specific to their target.

scholarly journals Tipping the Scales With Zebrafish to Understand Adaptive Tumor Immunity

2021 ◽  
Vol 9 ◽  
Author(s):  
Kelly Z. Miao ◽  
Grace Y. Kim ◽  
Grace K. Meara ◽  
Xiaodan Qin ◽  
Hui Feng
Keyword(s):  
Immune System ◽  
Tumor Immunity ◽  
Immune Cell ◽  
Driving Forces ◽  
Adaptive Immune System ◽  
Experimental System ◽  
Dynamic Interactions ◽  
Adaptive Immune ◽  
Anti Cancer ◽  
New Frontier

The future of improved immunotherapy against cancer depends on an in-depth understanding of the dynamic interactions between the immune system and tumors. Over the past two decades, the zebrafish has served as a valuable model system to provide fresh insights into both the development of the immune system and the etiologies of many different cancers. This well-established foundation of knowledge combined with the imaging and genetic capacities of the zebrafish provides a new frontier in cancer immunology research. In this review, we provide an overview of the development of the zebrafish immune system along with a side-by-side comparison of its human counterpart. We then introduce components of the adaptive immune system with a focus on their roles in the tumor microenvironment (TME) of teleosts. In addition, we summarize zebrafish models developed for the study of cancer and adaptive immunity along with other available tools and technology afforded by this experimental system. Finally, we discuss some recent research conducted using the zebrafish to investigate adaptive immune cell-tumor interactions. Without a doubt, the zebrafish will arise as one of the driving forces to help expand the knowledge of tumor immunity and facilitate the development of improved anti-cancer immunotherapy in the foreseeable future.

scholarly journals Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease

2021 ◽  
Vol 8 (5) ◽  
pp. e1036
Author(s):  
Zhaoqi Yan ◽  
Wei Yang ◽  
Hairong Wei ◽  
Marissa N. Dean ◽  
David G. Standaert ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Parkinson Disease ◽  
Peripheral Blood ◽  
Cytokine Production ◽  
Early Stage ◽  
Adaptive Immune System ◽  
Th2 Cells ◽  
Adaptive Immune

ObjectiveTo determine the activation status and cytokine profiles of CD4+ T cells, CD8+ T cells, and CD19+ B cells from patients with early-stage Parkinson disease (PD) compared with healthy controls (HCs).MethodsPeripheral blood samples from 41 patients with early-stage PD and 40 HCs were evaluated. Peripheral blood mononuclear cells were analyzed by flow cytometry for surface markers and intracellular cytokine production. Correlations of immunologic changes and clinical parameters were analyzed.ResultsAdaptive immunity plays a role in the pathogenesis of PD, yet the contribution of T cells and B cells, especially cytokine production by these cells, is poorly understood. We demonstrate that naive CD4+ and naive CD8+ T cells are significantly decreased in patients with PD, whereas central memory CD4+ T cells are significantly increased in patients with PD. Furthermore, IL-17–producing CD4+ Th17 cells, IL-4–producing CD4+ Th2 cells, and IFN-γ–producing CD8+ T cells are significantly increased in patients with PD. Regarding B cells, we observed a decrease in naive B cells and an increase in nonswitched memory and double-negative B cells. As well, TNF-α–producing CD19+ B cells were significantly increased in patients with PD. Notably, some of the changes observed in CD4+ T cells and B cells were associated with clinical motor disease severity.ConclusionsThese findings suggest that alterations in the adaptive immune system may promote clinical disease in PD by skewing to a more proinflammatory state in the early-stage PD patient cohort. Our study may shed light on potential immunotherapies targeting dysregulated CD4+ T cells, CD8+ T cells, and CD19+ B cells in patients with PD.

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