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European Journal of Cancer (Oxford,... Jan 2021Therapeutic cancer vaccination is an area of interest, even though promising efficacy has not been demonstrated so far. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Therapeutic cancer vaccination is an area of interest, even though promising efficacy has not been demonstrated so far.
DESIGN
A systematic review and meta-analysis was conducted to evaluate vaccines' efficacy on breast cancer (BC) and ovarian cancer (OC) patients. Our search was based on the PubMed electronic database, from 1st January 2000 to 4th February 2020.
OBJECTIVE
response rate (ORR) was the primary end-point of interest, while progression-free survival (PFS), overall survival (OS) and toxicity were secondary end-points. Analysis was performed separately for BC and OC patients. Pooled ORRs were estimated by fixed or random effects models, depending on the detected degree of heterogeneity, for all studies with more than five patients. Subgroup analyses by vaccine type and treatment schema as well as sensitivity analyses, were implemented.
RESULTS
Among 315 articles initially identified, 67 were eligible for our meta-analysis (BC: 46, 1698 patients; OC: 32, 426 patients; where both BC/OC in 11). Dendritic-cell and peptide vaccines were found in more studies, 6/10 BC and 10/13 OC studies, respectively. In our primary BC analysis (21 studies; 428 patients), the pooled ORR estimate was 9% (95%CI[5%,13%]). The primary OC analysis (12 studies; 182 patients), yielded pooled ORR estimate of 4% (95%CI[1%,7%]). Similar were the results derived in sensitivity analyses. No statistically significant differences were detected by vaccine type or treatment schema. Median PFS was 2.6 months (95% confidence interval (CI)[1.9,2.9]) and 13.0 months (95%CI[8.5,16.3]) for BC and OC respectively, while corresponding median OS was 24.8 months (95%CI[15.0,46.0]) and 39.0 months (95%CI[31.0,49.0]). In almost all cases, the observed toxicity was only moderate.
CONCLUSION
Despite their modest results in terms of ORR, therapeutic vaccines in the last 20 years display relatively long survival rates and low toxicity. Since a plethora of different approaches have been tested, a better understanding of the underlying mechanisms is needed in order to further improve vaccine efficacy.
Topics: Breast Neoplasms; Cancer Vaccines; Female; Humans; Ovarian Neoplasms; Time Factors
PubMed: 33221598
DOI: 10.1016/j.ejca.2020.10.014 -
Clinical NeuropharmacologyThe efficacy of dendritic cell vaccine for newly diagnosed glioblastoma remains controversial. We conduct a systematic review and meta-analysis to explore the influence... (Meta-Analysis)
Meta-Analysis
The efficacy of dendritic cell vaccine for newly diagnosed glioblastoma remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dendritic cell vaccine on treatment efficacy for newly diagnosed glioblastoma. We search PubMed, EMBASE, Web of science, EBSCO, and Cochrane library databases through December 2019 for randomized controlled trials assessing the efficacy and safety of dendritic cell vaccine for newly diagnosed glioblastoma. This meta-analysis is performed using the random effect model. Three randomized controlled trials are included in the meta-analysis. Overall, compared with control group for newly diagnosed glioblastoma, dendritic cell vaccine shows no substantial effect on median overall survival [standard mean difference, 0.11; 95% confidence interval (CI), -0.18 to 0.41; P = 0.45], median progression-free survival (standard mean difference, 0.12; 95% CI, -0.24 to 0.48; P = 0.50), progression-free survival rate [risk ratio (RR), 1.29; 95% CI, 0.82-2.04; P = 0.27], overall survival rate (RR, 1.29; 95% CI, 0.61-2.72; P = 0.50), or nervous system disorders (RR, 0.80; 95% CI, 0.59-1.08; P = 0.14). Dendritic cell vaccine may provide no obvious benefits for the newly diagnosed glioblastoma.
Topics: Dendritic Cells; Glioblastoma; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vaccines
PubMed: 34767325
DOI: 10.1097/WNF.0000000000000452 -
Journal of Hepatology Feb 2015The mononuclear phagocytic system (MPS), comprised of monocytes, macrophages, and dendritic cells, is essential in tissue homeostasis and in determining the balance of... (Review)
Review
The mononuclear phagocytic system (MPS), comprised of monocytes, macrophages, and dendritic cells, is essential in tissue homeostasis and in determining the balance of the immune response through its role in antigen presentation. It has been identified as a therapeutic target in infectious disease, cancer, autoimmune disease and transplant rejection. Here, we review the current understanding of the immunophenotype and function of the MPS in normal human liver. Using well-defined selection criteria, a search of MEDLINE and EMBASE databases identified 76 appropriate studies. The majority (n=67) described Kupffer cells (KCs), although the definition of KC differs between sources, and little data were available regarding their function. Only 10 papers looked at liver dendritic cells (DCs), and largely confirmed the presence of the major dendritic cell subsets identified in human blood. Monocytes were thoroughly characterized in four studies that utilized flow cytometry and fluorescent microscopy and highlighted their prominent role in liver homeostasis and displayed subtle differences from circulating monocytes. There was some limited evidence that liver DCs are tolerogenic but neither liver dendritic cell subsets nor macrophages have been thoroughly characterized, using either multi-colour flow cytometry or multi-parameter fluorescence microscopy. The lobular distribution of different subsets of liver MPS cells was also poorly described, and the ability to distinguish between passenger leukocytes and tissue resident cells remains limited. It was apparent that further research, using modern immunological techniques, is now required to accurately characterize the cells of the MPS in human liver.
Topics: Flow Cytometry; Humans; Immunity, Cellular; Immunophenotyping; Kupffer Cells; Liver; Mononuclear Phagocyte System; Reference Values
PubMed: 25315649
DOI: 10.1016/j.jhep.2014.10.006 -
Orphanet Journal of Rare Diseases Jan 2021Langerhans cell histiocytosis (LCH) is a rare disease that originates from the uncontrolled proliferation and accumulation of bone marrow-derived immature myeloid... (Review)
Review
BACKGROUND
Langerhans cell histiocytosis (LCH) is a rare disease that originates from the uncontrolled proliferation and accumulation of bone marrow-derived immature myeloid dendritic cells. Dendritic cells are a type of histiocyte that play an important role in the human immune system and are found in the bone, skin, stomach, eyes, intestines, and lungs.
OBJECTIVE
This systematic review aimed to collect and report published case reports of rare bone disease caused by LCH to avoid misdiagnoses or delays in diagnosis.
METHODS
We systematically searched Scopus, PubMed, Embase, and Web of Sciences from August 1, 2000 to December 31, 2019. Studies reporting cases of LCH with rare bone involvement were included.
RESULTS
We identified 60 articles including 64 cases. Of the identified cases, 31 (48.4%) involved children, and 33 (51.6%) involved adults. Additionally, 46.9% (30 individuals) were from Asian countries. The mean age of the children was 7.6 ± 4.3 years and that of the adults was 36 ± 12 years. The findings indicated that unifocal bone involvements were the most prevalent form of the disease (68.7%), and, overall, the skull and chest wall were the most commonly affected bones in both adults and children. The spine and long bones were the second most commonly affected bones in children, and the spine and jaw were the second most commonly affected bones in adults. Pain and swelling were the most frequent presenting signs among the investigated cases, and loss of consciousness, myelopathy, nerve palsy, visual loss, torticollis and clicking sounds were rare signs. Osteolytic lesions were the most frequent radiologic feature (62.5%), and intracranial hemorrhage, fluid-fluid level, dura and intracranial extension and pathologic fractures were rare radiological features. Total excision, curettage and observation in the unifocal group of patients and systemic chemotherapy in the other groups (i.e., multifocal and multisystem) were the most frequent management approaches. The recovery rates of the unifocal and multifocal groups were 77.3% and 81.8%, respectively, while that of the multisystem group was 55.5%. The rates of recurrence and mortality in the multisystem group were 11% and were higher than those in the other groups.
CONCLUSIONS
LCH is a rare disease that can affect any organ in the human body. However, bone is the most commonly involved organ, and rare bone involvements may be the first or only symptom of the disease due to the rarity of such lesions; a lack of familiarity with them may result in misdiagnosis or delayed diagnosis.
Topics: Adult; Asia; Bone Diseases; Child; Child, Preschool; Histiocytosis, Langerhans-Cell; Humans; Retrospective Studies; Skull
PubMed: 33388073
DOI: 10.1186/s13023-020-01625-z -
Cureus Aug 2023Tumor necrosis factor-alpha (TNF-α) inhibitors have been shown to be well tolerated among patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis.... (Review)
Review
Tumor necrosis factor-alpha (TNF-α) inhibitors have been shown to be well tolerated among patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Meanwhile, more recently, clinical practice and research efforts have uncovered increasing cases of psoriatic lesion development tied to initiating treatment with a TNF-α inhibitor. The underlying mechanisms associated with this occurrence have yet to be fully elucidated. A review and analysis of cases of paradoxical psoriasis currently published in the literature is warranted. In addition, exploring possible mechanisms of action and potential treatment options associated with favorable outcomes is much needed. A systematic literature review was performed utilizing PubMed and Google Scholar databases (1992-present), in which 106 cases of paradoxical psoriasis were reviewed. The most common morphology developed was plaque psoriasis vulgaris. There was a female predominance (61.3%), and the most common underlying autoimmune disease was rheumatoid arthritis (45.3%). In addition, the most commonly associated drug with the onset of psoriatic lesions was infliximab (62.3%). Furthermore, the findings suggest that the most well-supported mechanism of action involves the uncontrolled release of interferon-alpha (IFN-α) from plasmacytoid dendritic cells (pDCs) after TNF-α inhibition. While TNF-α inhibitors have been shown to have great benefits to patients with rheumatologic diseases, cases of paradoxical psoriasis demonstrate the importance of close monitoring of patients on TNF-α inhibitors to allow for early recognition, treatment, and potentially change to a different mechanism of action of the medication used to prevent further progression of the inflammatory lesions.
PubMed: 37664349
DOI: 10.7759/cureus.42791 -
Journal of Medical Virology Jan 2016Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Dendritic cells (DCs), as the most efficient professional... (Review)
Review
Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Dendritic cells (DCs), as the most efficient professional antigen-presenting cells (APCs), possess the strongest antigen presenting the effect in the body and can stimulate the initial T cell activation and proliferation. DCs of patients with chronic HBV infection are impaired, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence. Recently, numerous methods have been developed to induce DCs maturation. To date, recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) combined with interleukin-4 (rhIL-4) has been a classic culture combination to DCs. The recently classified type III interferon group interferon-λ (IFN-λ) displays antiviral, antitumor, and immunoregulatory activity. In our laboratory, we demonstrate that IFN-λ1 combined with rhGM-CSF and rhIL-4 can significantly increase the expression of DC surface molecules and the secretion of interleukin-12 (IL-12) and interferon-γ (IFN-γ) in patients with chronic hepatitis B infection. In this review, we emphasize on the role of DCs in the immunopathogenesis of chronic HBV infection. Importantly, we systematic review that the latest update in the current status of knowledge on the methods of inducing DCs maturation in anti-HBV immunity. What's more, we conclude that IFN-λ1 combined with GM-CSF and IL-4 can induce DCs maturation, which could become a possibility to be applied to the autologus dendritic cell vaccine to treat chronic hepatitis B.
Topics: Dendritic Cells; Hepatitis B virus; Hepatitis B, Chronic; Host-Pathogen Interactions; Humans; Immune Tolerance; Immunologic Factors
PubMed: 26104380
DOI: 10.1002/jmv.24306 -
Autoimmunity Reviews Jan 2018Significant advances in the understanding of the molecular basis of innate immunity have led to the identification of interferons (IFNs), particularly IFN-α, as central... (Review)
Review
Significant advances in the understanding of the molecular basis of innate immunity have led to the identification of interferons (IFNs), particularly IFN-α, as central mediators in the pathogenesis of Systemic Lupus Erythematosus. Therefore, targeting of IFNs and of their downstream pathways has emerged as important developments for novel drug research in SLE. Based on this, several specific interferon blocking strategies using anti-IFN-α antibodies, anti-type I interferon receptor antibodies, Interferon-α-kinoid, or anti-IFN-γ antibodies have all been assessed in recent clinical trials. Alternative strategies targeting the plasmacytoid dendritic cells (pDCs), Toll-Like Receptors (TLRs)-7/9 or their downstream pathways such as the myeloid differentiation primary-response protein 88 (MYD88), spleen tyrosine kinase (Syk), Janus-kinases (JAKs), interleukin-1 receptor-associated kinase 4 (IRAK4), or the Tyrosine Kinase 2 (TYK2) are also investigated actively in SLE, at more preliminary clinical development stages, except for JAK inhibitors which have reached phase 2 studies. In a near future, in-depth and personalized functional characterization of IFN pathways may provide further guidance for the selection of the most relevant therapeutic strategy in SLE, tailored at the patient-level.
Topics: Humans; Interferons; Lupus Erythematosus, Systemic
PubMed: 29108825
DOI: 10.1016/j.autrev.2017.11.009 -
British Journal of Cancer Apr 2019Various immune cells have been suggested as prognostic markers for cancer patients. In this article, we present a systematic review and meta-analysis of studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Various immune cells have been suggested as prognostic markers for cancer patients. In this article, we present a systematic review and meta-analysis of studies assessing the prognostic value of tissue-infiltrating immune cells in oral cancer and discuss the reporting quality of these studies.
METHODS
We performed a systematic literature search and included studies using immunohistochemistry and survival analysis to assess the prognostic value of tumour-infiltrating T cells, B cells, macrophages, dendritic cells, mast cells and natural killer cells in oral cancer. We performed meta-analysis of studies providing necessary statistical data and investigated the studies' adherence to the REporting recommendations for tumour MARKer prognostic studies (REMARK) guidelines.
RESULTS
Of the 1960 articles identified, 33 were eligible for this systematic review and 8 were included in the meta-analysis. CD163+ M2 macrophages and CD57+ natural killer cells were the most promising predictors of survival in oral cancer patients. Many studies lacked important information on their design and conduct.
CONCLUSION
Deficiencies in the reporting of study design and conduct make it difficult to draw reliable conclusions about the suggested markers. The prognostic value of CD163+ M2 macrophages and CD57+ natural killer cells should be validated in large, standardised studies.
Topics: B-Lymphocytes; Dendritic Cells; Humans; Killer Cells, Natural; Lymphocytes, Tumor-Infiltrating; Macrophages; Mast Cells; Mouth Neoplasms; Prognosis; Squamous Cell Carcinoma of Head and Neck; T-Lymphocytes
PubMed: 30808992
DOI: 10.1038/s41416-019-0409-6 -
Experimental Gerontology Jul 2021Immunosenescence is a remodeling of the immune system occurring with aging that leads to an increased susceptibility to auto-immunity, infections and reduced vaccination... (Review)
Review
Immunosenescence is a remodeling of the immune system occurring with aging that leads to an increased susceptibility to auto-immunity, infections and reduced vaccination response. A growing consensus supports the view that physical exercise may counteract immunosenescence and improve the immune response. Unfortunately, evidence regarding the effects of exercise on markers of cellular immunosenescence lacked uniformity at the time of an extensive literature review in 2016. Moreover, exercise-induced effects in older adults were underrepresented compared to young adults or completely lacking, such as for senescent T-cells and apoptosis of T-lymphocytes. The aim of this systematic literature study was to collect and appraise newly available data regarding exercise-induced changes on immunosenescence-related markers of immune cells and compare this against data that was already available in 2016. Systematic reviewing of newly available data in the field of exercise immunology provides additional evidence for the effect of exercise on immunosenescence-related cellular markers. Importantly, this review provides evidence for the effect of long-term exercise on senescent T-lymphocytes in older adults. Additionally, newly retrieved evidence shows an acute exercise-induced mobilization of naïve and memory cells in older adults. In general, data regarding long-term exercise-induced effects in older adults remain scarce. Noteworthy was the high number of articles describing exercise-induced effects on regulatory T-cells. However exercise-induced effects on this cell type are still inconclusive as some articles reported an exercise-induced up- or downregulation, while others reported no effects at all. Numerous studies on Natural Killer cell counts did not provide uniformity among data that was already available. Recent data regarding dendritic cells mostly described an increase after exercise. Overall, our literature update highlights the major influence of the type and intensity of exercise on immunosenescence-related markers, especially in older adults.
Topics: Biomarkers; Exercise; Immune System; Immunosenescence
PubMed: 33794319
DOI: 10.1016/j.exger.2021.111318 -
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