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Mediators of Inflammation 2020Langerhans cells (LCs) are bone marrow-derived dendritic cells (DCs) that represent 2-3% of the entire cell population of the human skin, known to have an ability to...
Langerhans cells (LCs) are bone marrow-derived dendritic cells (DCs) that represent 2-3% of the entire cell population of the human skin, known to have an ability to present antigens to T lymphocytes. Moreover, there is evidence that LCs are probably capable of inducing the local cytotoxic type T-cell-mediated response against the tumour-associated antigens. In the past two decades, a dramatic increase has been noted in the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The purpose of this study was to critically assess the results of available studies quantitatively assessing the LCs in nonmelanoma skin cancers and try to establish a conclusion of its possible impact on their future treatment. The PubMed, EMBASE, and the Web of Science databases were searched, which returned 948 citations. After a thorough analysis of full article texts, 30 studies have been chosen, including 11 of the BCC, 12 of the SCC specimens, and 7 analysing both tumour types. There was an overall trend towards slightly higher numbers of LCs in BCC than in SCC; however, these tendencies were discrepant between the studies. We presume that such differences could be caused by various staining techniques with a broad spectrum of specificity, including anti-S100, anti-CD1a, and ATPase activity staining used for LCs identification. We hypothesise that as there is a high inconsistency between the results of the studies, as far as the densities of LCs observed in the specimens are concerned, it seems that the mechanism of the influence of LCs on the antitumoural immune response is complicated. Finally, as at present, there is a paucity of available risk scores for the recurrence or progression of BCC or SCC, the creation of classification stratifying that risk including the density of LCs could bring additional information both for the physician and the patient.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Count; Humans; Langerhans Cells; Skin Neoplasms
PubMed: 32377167
DOI: 10.1155/2020/8745863 -
BMC Cancer Apr 2020This study aimed to investigate the efficacy and safety of cytokine-induced killer (CIK)/dendritic cell combined with CIK (DC-CIK) cell therapy in advanced... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aimed to investigate the efficacy and safety of cytokine-induced killer (CIK)/dendritic cell combined with CIK (DC-CIK) cell therapy in advanced gastrointestinal cancer (GIC).
METHODS
The PubMed, Cochrane library, and Embase were searched to conduct a meta-analysis of clinical controlled trials to evaluate the efficacy and safety of CIK/DC-CIK cell therapy in advanced GIC. The pooled risk ratios (RRs) or weighted mean difference (WMD) with 95% confidence intervals (95% CIs) were calculated.
RESULTS
A total of nine studies with 1113 patients were identified. The overall survival (RR = 1.84, 95% CI = 1.41-2.40, P = 0.654, I = 0%), progression-free survival (RR = 1.99, 95% CI = 1.52-2.60, P = 0.727, I = 0%), and quality of life (WMD = 16.09, 95% CI = 1.66-30.52, P < 0.001, I = 98.8%) were significantly improved in patients who received chemotherapy combined with CIK/DC-CIK cells, and no severe adverse events were reported.
CONCLUSION
This meta-analysis suggested that the combination of CIK/DC-CIK immunotherapy and chemotherapy was safe and applicable for patients with advanced GIC. It is a feasible choice to prolong survival and improve quality of life.
Topics: Cytokine-Induced Killer Cells; Dendritic Cells; Gastrointestinal Neoplasms; Humans; Immunologic Factors; Immunotherapy, Adoptive; Prognosis
PubMed: 32345239
DOI: 10.1186/s12885-020-06860-y -
PLoS Pathogens Mar 2020Trichuris trichiura is a parasite that infects 500 million people worldwide, leading to colitis, growth retardation and Trichuris dysentery syndrome. There are no... (Meta-Analysis)
Meta-Analysis
Trichuris trichiura is a parasite that infects 500 million people worldwide, leading to colitis, growth retardation and Trichuris dysentery syndrome. There are no licensed vaccines available to prevent Trichuris infection and current treatments are of limited efficacy. Trichuris infections are linked to poverty, reducing children's educational performance and the economic productivity of adults. We employed a systematic, multi-stage process to identify a candidate vaccine against trichuriasis based on the incorporation of selected T-cell epitopes into virus-like particles. We conducted a systematic review to identify the most appropriate in silico prediction tools to predict histocompatibility complex class II (MHC-II) molecule T-cell epitopes. These tools were used to identify candidate MHC-II epitopes from predicted ORFs in the Trichuris genome, selected using inclusion and exclusion criteria. Selected epitopes were incorporated into Hepatitis B core antigen virus-like particles (VLPs). Bone marrow-derived dendritic cells and bone marrow-derived macrophages responded in vitro to VLPs irrespective of whether the VLP also included T-cell epitopes. The VLPs were internalized and co-localized in the antigen presenting cell lysosomes. Upon challenge infection, mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden, and mounted Trichuris-specific IgM and IgG2c antibody responses. The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia. Collectively our data establishes that a combination of in silico genome-based CD4+ T-cell epitope prediction, combined with VLP delivery, offers a promising pipeline for the development of an effective, safe and affordable helminth vaccine.
Topics: Animals; Antibodies, Helminth; Computer Simulation; Dendritic Cells; Epitopes, T-Lymphocyte; Histocompatibility Antigens Class II; Humans; Immunogenicity, Vaccine; Macrophages; Male; Mice; Mice, Inbred C57BL; Trichuriasis; Trichuris; Vaccines
PubMed: 32203551
DOI: 10.1371/journal.ppat.1008243 -
Cells Sep 2019To review the current knowledge regarding the involvement of human papilloma virus (HPV) infection and the immune system in the development of head and neck squamous...
OBJECTIVES
To review the current knowledge regarding the involvement of human papilloma virus (HPV) infection and the immune system in the development of head and neck squamous cell carcinoma (HNSCC).
METHODS
An electronic literature search was conducted to identify articles published between 1990 and 2019 pertaining to tumor-infiltrating immune cells (TICs) in HNSCC using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Issues of clinical relevance, including tumor location, the number of tumor samples, the inclusion of additional specimens (dysplastic or normal mucosa), tumor size, methods used for HPV detection, relationship between antigen expression and patient characteristics (age, gender, smoking, alcohol consumption, etc.), and prognostic data (overall survival (OS) and recurrence-free survival (RFS)) were assessed by four blinded investigators.
RESULTS
The search identified 335 relevant studies, of which 41 met the inclusion criteria. Of these, 7 studies focused on the peripheral blood immune cell concentration in patients with HNSCC according to HPV status, and 36 studies investigated TICs in the intraepithelial and/or stromal compartment(s) according to HPV status. The immune cells studied were CD8+ T cells (N = 19), CD4+ T cells (N = 7), regulatory T cells (Tregs, N = 15), macrophages (N = 13), myeloid-derived suppressor cells (MDSCs, N = 4), and Langerhans cells (LCs, N = 2).
CONCLUSIONS
Irrespective of tumor location, CD8+ and CD4+ T cells appear to play a key role in the development of HPV-related HNSCC, and their infiltration is likely associated with a significant impact on OS and RFS. To date, the roles and prognostic value of Tregs, macrophages, DCs and MDSCs remain unclear.
Topics: Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Langerhans Cells; Macrophages; Male; Myeloid-Derived Suppressor Cells; Oropharyngeal Neoplasms; Oropharynx; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck; T-Lymphocytes, Regulatory
PubMed: 31510065
DOI: 10.3390/cells8091061 -
Journal of the International AIDS... Aug 2019Hepatitis C virus (HCV) is a major public health threat. Although the recent availability of highly effective directly acting antivirals created optimism towards HCV...
INTRODUCTION
Hepatitis C virus (HCV) is a major public health threat. Although the recent availability of highly effective directly acting antivirals created optimism towards HCV elimination, there is ongoing transmission of HCV in men who have sex with men (MSM). We here report current epidemiological trends and synthesise evidence on behavioural, network, cellular and molecular host factors associated with sexual transmission of HCV, in particular the role of HIV-1 co-infection. We discuss prevention opportunities focusing on the potential of HCV treatment.
METHODS
We searched MEDLINE, fact sheets from health professional bodies and conference abstracts using appropriate keywords to identify and select relevant reports.
RESULTS AND DISCUSSION
Recent studies strongly suggest that HCV is transmitted via sexual contact in HIV-positive MSM and more recently in HIV-negative MSM eligible for or on pre-exposure prophylaxis. The reinfection risk following clearance is about 10 times the risk of primary infection. International connectedness of MSM transmission networks might contribute to ongoing reinfection. Some of these networks might overlap with networks of people who inject drugs. Although, the precise mechanisms facilitating sexual transmission remain unclear, damage to the mucosal barrier in the rectum could increase susceptibility. Mucosal dendritic cell subsets could increase HCV susceptibility by retaining HCV and transmitting the virus to other cells, allowing egress into blood and liver. Early identification of new HCV infections is important to prevent onward transmission, but early diagnosis of acute HCV infection and prompt treatment is hampered by the slow rate of HCV antibody seroconversion, which in rare cases may take more than a year. Novel tests such as testing for HCV core antigen might facilitate early diagnosis.
CONCLUSIONS
High-risk sexual behaviour, network characteristics, co-infection with sexually transmitted infections like HIV-1 and other concomitant bacterial and viral sexually transmitted infections are important factors that lead to HCV spread. Targeted and combined prevention efforts including effective behavioural interventions and scale-up of HCV testing and treatment are required to halt HCV transmission in MSM.
Topics: Coinfection; HIV Infections; HIV-1; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Male; Sexual and Gender Minorities; Sexually Transmitted Diseases
PubMed: 31468692
DOI: 10.1002/jia2.25348 -
World Journal of Gastroenterology Jul 2019Hepatocellular carcinoma (HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatocellular carcinoma (HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy, including dendritic cells (DCs) and cytokine-induced killer cells (CIKs), has brought HCC patients an effective benefit. However, the efficacy and necessity of cellular immunotherapy after different interventional therapy remains to be further explored.
AIM
To investigate the efficacy of cellular immunotherapy, involving DCs and CIKs, combined with different conventional treatments of HCC.
METHODS
We performed a literature search on PubMed and Web of Science up to February 15, 2019. Long-term efficacy (overall survival and recurrence) and short-term adverse effects were investigated to assess the effectiveness of immunotherapy with DCs and/or CIKs. Review Manager 5.3 was used to perform the analysis.
RESULTS
A total of 22 studies involving 3756 patients selected by eligibility inclusion criteria were forwarded for meta-analysis. Combined with the conventional clinical treatment, immunotherapy with DCs and/or CIKs was demonstrated to significantly improve overall survival at 6 mo [risk ratio (RR) = 1.07; 95% confidence interval (CI): 1.01-1.13, = 0.02], 1 year (RR = 1.12; 95%CI: 1.07-1.17, < 0.00001), 3 years (RR = 1.23; 95%CI: 1.15-1.31, < 0.00001) and 5 years (RR = 1.26; 95%CI: 1.15-1.37, < 0.00001). Recurrence rate was significantly reduced by cellular immunotherapy at 6 mo (RR = 0.50; 95%CI: 0.36-0.69, < 0.0001) and 1 year (RR = 0.82; 95%CI: 0.75-0.89, < 0.00001). Adverse effect assessment addressed that immunotherapy with DCs and/or CIKs was accepted as a safe, feasible treatment.
CONCLUSION
Combination immunotherapy with DCs, CIKs and DC/CIK with various routine treatments for HCC was evidently suggested to improve patients' prognosis by increasing overall survival and reducing cancer recurrence.
Topics: Carcinoma, Hepatocellular; Clinical Trials as Topic; Combined Modality Therapy; Cytokine-Induced Killer Cells; Dendritic Cells; Feasibility Studies; Humans; Immunotherapy, Adoptive; Liver Neoplasms; Neoplasm Recurrence, Local; Prognosis; Survival Analysis; Treatment Outcome
PubMed: 31367163
DOI: 10.3748/wjg.v25.i27.3649 -
F1000Research 2018Hidradenitis suppurativa (HS) is a chronic inflammatory disease with significant morbidity and impact on quality of life. Our understanding of the pathophysiology is...
Hidradenitis suppurativa (HS) is a chronic inflammatory disease with significant morbidity and impact on quality of life. Our understanding of the pathophysiology is incomplete, impairing efforts to develop novel therapeutic targets. Immunohistochemistry studies have produced conflicting results and no systematic evaluation of study methods and results has been undertaken to date. This systematic review aimed to collate and describe all reports of immunohistochemical staining in HS. This systematic review was registered with PROSPERO and conducted in line with the PRISMA reporting guidelines. Potential bias was assessed using the NIH Criteria and antibodies used across various studies were tabulated and compared. : A total of 22 articles were identified describing results from 494 HS patients and 168 controls. 87 unique immunohistochemical targets were identified. The overall quality of studies was sub-optimal with staining intensity confounded by active treatment. Conflicting data was identified and able to be reconciled through critical evaluation of the study methodology. : Keratinocyte hyperplasia with loss of cytokeratin markers co-localizes with inflammation comprising of dendritic Cells, T-lymphocytes and macrophages, which are known to play central roles in inflammation in HS. Primary follicular occlusion as a pathogenic paradigm and the principal driver of HS is unclear based upon the findings of this review. Inflammation as a primary driver of disease with secondary hyperkeratosis and follicular occlusion is more consistent with the current published data.
Topics: Animals; Desmocollins; Female; Hidradenitis Suppurativa; Humans; Hyperplasia; Inflammation; Keratosis; Male; Membrane Glycoproteins; Mice; Quality of Life; Ubiquitin-Protein Ligases
PubMed: 31281635
DOI: 10.12688/f1000research.17268.2 -
Critical Care (London, England) Jun 2019Brain injury (BI) induces a state of immunodepression leading to pneumonia. We investigated the invariant natural killer T (iNKT) cell compartment. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Brain injury (BI) induces a state of immunodepression leading to pneumonia. We investigated the invariant natural killer T (iNKT) cell compartment.
METHODS
This is an observational study in two surgical intensive care units (ICUs) of a single institution and a research laboratory. Clinical data and samples from a prospective cohort were extracted. Severe brain-injured patients (n = 33) and sex- and age-matched healthy donors (n = 40) were studied.
RESULTS
We observed the presence of IL-10 in serum, a loss of IFN-γ and IL-13 production by peripheral blood mononuclear cells (PBMCs) following IL-2 stimulation, and downregulation of HLA-DR expression on both monocytes and B cells early after BI. Inversely, CD1d, the HLA class I-like molecule involved in antigen presentation to iNKT cells, was over-expressed on patients' monocytes and B cells. The antigen-presenting activity to iNKT cells of PBMCs was increased in the patients who developed pneumonia, but not in those who remained free of infection. Frequencies of iNKT cells among PBMCs were dramatically decreased in patients regardless of their infection status. Following amplification, an increased frequency of CD4+ iNKT cells producing IL-4 was noticed in the group of patients free of infection compared with those who became infected and with healthy donors. Finally, serum from BI patients inhibited the iNKT cells' specific response as well as the non-specific IL-2 stimulation of PBMCs, and the expression of the beta-2 adrenergic receptor was elevated at the surface of patients T lymphocytes.
CONCLUSIONS
We observed severe alterations of the iNKT cell compartment, including the presence of inhibitory serum factors. We demonstrate for the first time that the decreased capacity to present antigens is not a generalized phenomenon because whereas the expression of HLA-DR molecules is decreased, the capacity for presenting glycolipids through CD1d expression is higher in patients.
Topics: Brain Injuries; Cardiotonic Agents; Cell Compartmentation; Fluid Therapy; Humans; Natural Killer T-Cells
PubMed: 31253189
DOI: 10.1186/s13054-019-2518-2 -
Experimental Gerontology Sep 2019Immunosenescence contributes to a decreased capacity of the immune system to respond effectively to infections or vaccines in the elderly. The full extent of the...
Immunosenescence contributes to a decreased capacity of the immune system to respond effectively to infections or vaccines in the elderly. The full extent of the biological changes that lead to immunosenescence are unknown, but numerous cell types involved in innate and adaptive immunity exhibit altered phenotypes and function as a result of aging. These manifestations of immunosenescence at the cellular level are mediated by dysregulation at the genetic level, and changes throughout the immune system are, in turn, propagated by numerous cellular interactions. Environmental factors, such as nutrition, also exert significant influence on the immune system during aging. While the mechanisms that govern the onset of immunosenescence are complex, systems biology approaches allow for the identification of individual contributions from each component within the system as a whole. Although there is still much to learn regarding immunosenescence, systems-level studies of vaccine responses have been highly informative and will guide the development of new vaccine candidates, novel adjuvant formulations, and immunotherapeutic drugs to improve vaccine responses among the aging population.
Topics: Adaptive Immunity; Aged; B-Lymphocytes; Dendritic Cells; Humans; Immune System; Immunity, Innate; Immunosenescence; Systems Biology; T-Lymphocytes; Vaccination
PubMed: 31201918
DOI: 10.1016/j.exger.2019.110632 -
Schizophrenia Bulletin Feb 2020Changed synapse density has been suggested to be involved in the altered brain connectivity underlying schizophrenia (SCZ) pathology. However, postmortem studies... (Meta-Analysis)
Meta-Analysis
Changed synapse density has been suggested to be involved in the altered brain connectivity underlying schizophrenia (SCZ) pathology. However, postmortem studies addressing this topic are heterogeneous and it is not known whether changes are restricted to specific brain regions. Using meta-analysis, we systematically and quantitatively reviewed literature on the density of postsynaptic elements in postmortem brain tissue of patients with SCZ compared to healthy controls. We included 3 outcome measurements for postsynaptic elements: dendritic spine density (DSD), postsynaptic density (PSD) number, and PSD protein expression levels. Random-effects meta-analysis (31 studies) revealed an overall decrease in density of postsynaptic elements in SCZ (Hedges's g: -0.33; 95% CI: -0.60 to -0.05; P = .020). Subgroup analyses showed reduction of postsynaptic elements in cortical but not subcortical tissues (Hedges's g: -0.44; 95% CI: -0.76 to -0.12; P = .008, Hedges's g: -0.11; 95% CI: -0.54 to 0.35; P = .671) and specifically a decrease for the outcome measure DSD (Hedges's g: -0.81; 95% CI: -1.37 to -0.26; P = .004). Further exploratory analyses showed a significant decrease of postsynaptic elements in the prefrontal cortex and cortical layer 3. In all analyses, substantial heterogeneity was present. Meta-regression analyses showed no influence of age, sex, postmortem interval, or brain bank on the effect size. This meta-analysis shows a region-specific decrease in the density of postsynaptic elements in SCZ. This phenotype provides an important cellular hallmark for future preclinical and neuropathological research in order to increase our understanding of brain dysconnectivity in SCZ.
Topics: Brain; Humans; Schizophrenia; Synapses
PubMed: 31192350
DOI: 10.1093/schbul/sbz060