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Autoimmunity Reviews Dec 2012To evaluate whether vitamin D levels are related to the risk of developing autoimmune diseases and whether supplementation with vitamin D can modify the course of the... (Review)
Review
OBJECTIVE
To evaluate whether vitamin D levels are related to the risk of developing autoimmune diseases and whether supplementation with vitamin D can modify the course of the diseases.
METHODS
We reviewed the most relevant papers published from January 1973 to October 2011, using Medline and EMBASE and the search terms "vitamin D"; "autoimmune disease"; "autoimmunity"; "rheumatoid arthritis"; "systemic lupus erythematosus"; "scleroderma"; "systemic sclerosis"; "type 1 diabetes"; "multiple sclerosis"; and "undifferentiated connective tissue disease". We selected studies on the environmental, genetic and epidemiologic association of vitamin D with autoimmune diseases. Using the strategy described, we identified 1268 articles. 331 articles were eliminated on the basis of the title and another 703 on the basis of the abstract, since they were considered irrelevant for the purposes of the study. Full-text examination was performed on the remaining 234 studies, and a further 15 studies were excluded from the review, since the results had been confirmed or superseded by more recent research. Finally, a systematic review was conducted on 219 articles concerning cross-sectional data on: vitamin D levels and autoimmune diseases; interventional data on vitamin D supplementation in autoimmune diseases; prospective data linking vitamin D level or intake to autoimmune disease risk.
RESULTS
Physiopathology studies confirm that hypovitaminosis D, in genetically predisposed subjects, can impair self tolerance by compromising the regulation of dendritic cells, of regulatory T-lymphocytes and of Th1 cells. Cross-sectional studies show that levels of vitamin D <30 ng/mL are present in a significant percentage, not only in patients with autoimmune disease, but also in healthy subjects (30-77%), and link profound deficiency (<10 ng/mL) with aggravation of symptomatology, while genetic studies associate polymorphism of vitamin D receptors to various autoimmune diseases. Among experimental studies on humans, only those on type-1 diabetes prove that the risks are significantly reduced in infants treated with vitamin D after the 7th month (OR 0.71, 95% CI, 0.60 to 0.84) and that a dose-response effect exists.
CONCLUSIONS
Basic, genetic, and epidemiological studies indicate a potential role of vitamin D in the prevention of autoimmune diseases, but randomized and controlled trials are necessary to establish the clinical efficacy of vitamin D supplementation in ill or at-risk subjects.
Topics: Autoimmune Diseases; Dietary Supplements; Environment; Gene-Environment Interaction; Genetic Association Studies; Humans; Prevalence; Vitamin D
PubMed: 22776787
DOI: 10.1016/j.autrev.2012.07.007 -
International Journal of Molecular... Nov 2016The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic... (Meta-Analysis)
Meta-Analysis Review
The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%-51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.
Topics: AIDS Vaccines; Clinical Trials as Topic; Dendritic Cells; HIV Infections; Humans; Immunotherapy
PubMed: 27898045
DOI: 10.3390/ijms17121985 -
Frontiers in Immunology 2021Immune checkpoint inhibitors (ICIs) have been widely used in hepatocellular carcinoma (HCC), while only a subset of patients experience clinical benefit. We aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Immune checkpoint inhibitors (ICIs) have been widely used in hepatocellular carcinoma (HCC), while only a subset of patients experience clinical benefit. We aimed to investigate the effects of viral etiology on response to ICIs in HCC and depict the tumor immune microenvironment (TIME) of virally infected and uninfected HCC.
METHODS
A systematic search was conducted in PubMed, Web of Science, Embase, and the Cochrane central register of controlled trials up to August 2021. Clinical trials reporting the efficacy of ICIs in HCC were eligible. Baseline characteristics including first author, year of publication, National Clinical Trials (NCT) registry number, study region, sample sizes, interventions, line of treatment, and viral status were extracted. Meta-analysis was conducted to generate combined odds ratios (ORs) with 95% confidence intervals (CI) based on random or fixed effect model, depending on heterogeneity. Tumor immune microenvironment was depicted using ESTIMATE and CIBERSORT algorithm.
RESULTS
Eight studies involving 1,520 patients were included. Combined data suggested that there was no significant difference of objective response rate (ORR) between virally infected HCC and non-viral HCC patients [OR = 1.03 (95% CI, 0.77-1.37; I = 30.9%, p = 0.152)]. Similarly, difference was not observed on ORR between HBV-HCC and HCV-HCC patients [OR = 0.74 (95% CI, 0.52-1.06; I = 7.4%, p = 0.374)]. The infiltration of immune cells in the tumor microenvironment did not differ by etiology except for M0 macrophages, M2 macrophages, regulatory T cells, naive B cells, follicular helper T cells, activated dendritic cells, activated mast cells, and plasma cells. Despite differences in infiltration observed in specific cell types, the immune score and stromal score were generally comparable among etiology groups.
CONCLUSION
Viral etiology may not be considered as the selection criteria for patients receiving ICIs in HCC, and viral status has little impact on TIME remodeling during HCC tumorigenesis.
Topics: Animals; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Liver Neoplasms; Tumor Microenvironment
PubMed: 34659220
DOI: 10.3389/fimmu.2021.733530 -
Prostate International Dec 2018Dendritic cells (DCs) are used in many malignancies as vaccines to induce immunity against specific cancer antigens. The role of DCs in metastatic castration-resistant... (Review)
Review
BACKGROUND
Dendritic cells (DCs) are used in many malignancies as vaccines to induce immunity against specific cancer antigens. The role of DCs in metastatic castration-resistant prostate cancer (mCRPC) is not determined. In this study, the proportion of mCRPC patients with clinically significant response to targeted therapy by DCs pulsed with prostate-specific membrane antigen was evaluated, and the possible adverse effects of this modality were investigated.
METHODS
Major databases were searched up to Feb 2017, to identify studies in which the antitumor efficacy of DCs pulsed with the extracellular portion of PSMA was studied for the treatment of mCRPC. Data were collected by two reviewers and analyzed using Comprehensive Meta-Analysis software, version 2.0.
FINDINGS
Our study consisted of 6 nonrandomized prospective (cohort) trials, overall reporting on 153 mCRPC patients. The event rate that is the representative of fraction of patients showing antitumor response was 0.43 (95% confidence interval = 0.355-0.512; = 0.097). No significant between-study heterogeneity or inconsistency was detected (I = 5.47; Q = 5; = 0.382). Our study failed to demonstrate a significant therapeutic efficacy for DCs in mCRPC. However, no significant adverse effects were seen.
PubMed: 30505813
DOI: 10.1016/j.prnil.2018.04.001 -
Life Sciences Jan 2021Although anti-inflammatory properties are attributed to sesquiterpene lactones (SL), cutaneous hypersensitivity reactions are proposed as limitations for SL-based...
Although anti-inflammatory properties are attributed to sesquiterpene lactones (SL), cutaneous hypersensitivity reactions are proposed as limitations for SL-based therapies. Thus, the impact of SL on the skin and skin-related cells was systematically reviewed. Studies indexed in electronic databases were screened from the PRISMA strategy. The risk of bias in all studies was verified from the SYRCLE's tool. Thirty original studies were recovered and analyzed. Mice and guinea pig, keratinocytes and fibroblasts were predominantly investigated from in vivo and in vitro studies, respectively. In vivo studies indicated that most SL induced contact dermatitis associated with edema, erythema, and inflammatory infiltrate. Conversely, in vitro evidence was consistent with a dose-dependent anti-inflammatory effect of SL in response to reduced cytokines, 5-LOX, and COX-2 levels or activity in keratinocytes, fibroblasts, macrophages and dendritic cells; which are events potentially triggered by downregulation of gene expression and/or inhibition of the NF-κB signaling pathway. In vivo studies presented uncertain to high-risk of bias mainly associated with underreporting of randomization and experimental blinding. The current evidence supports potent cutaneous immunomodulatory properties of SL. Although in vitro and in vivo studies indicate opposite anti- or proinflammatory effects, this contradiction exhibits a dose-dependent component. In addition, the anti-inflammatory pathways activated by SL are better understood from in vitro evidence. However, additional studies are required to elucidating specific anti-inflammatory and proinflammatory mechanisms triggered by SL in vivo. Thus, controlling the sources of bias described in this review can contribute to improving the quality of the evidence in further investigations.
Topics: Animals; Anti-Inflammatory Agents; Dermatitis, Contact; Dose-Response Relationship, Drug; Guinea Pigs; Humans; Lactones; Mice; NF-kappa B; Sesquiterpenes; Skin
PubMed: 33278385
DOI: 10.1016/j.lfs.2020.118815 -
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 -
Oncology Reviews 2024Malignant gliomas are known with poor prognosis and low rate of survival among brain tumors. Resection surgery is followed by chemotherapy and radiotherapy in treatment...
BACKGROUND
Malignant gliomas are known with poor prognosis and low rate of survival among brain tumors. Resection surgery is followed by chemotherapy and radiotherapy in treatment of gliomas which is known as the conventional treatment. However, this treatment method results in low survival rate. Vaccination has been suggested as a type of immunotherapy to increase survival rate of glioma patients. Different types of vaccines have been developed that are mainly classified in two groups including peptide vaccines and cell-based vaccines. However, there are still conflicts about which type of vaccines is more efficient for malignant glioma treatment.
METHODS
Phase Ⅰ/Ⅱ clinical trials which compared the efficacy and safety of various vaccines with conventional treatments were searched in databases through November 2022. Overall survival (OS) rate, progression free survival (PFS), and OS duration were used for calculation of pooled risk ratio (RR). In addition, fatigue, headache, nausea, diarrhea, and flu-like syndrome were used for evaluating the safety of vaccines therapy in glioma patients.
RESULTS
A total of twelve articles were included in the present meta-analysis. Comparison of OS rate between vaccinated groups and control groups who underwent only conventional treatments showed a significant increase in OS rate in vaccinated patients (I = 0%, RR = 11.17, 95% CI: 2.460-50.225). PFS rate was better in vaccinated glioma patients (I = 83%, RR = 2.87, 95% CI: 1.63-5.03). Assessment of safety demonstrated that skin reaction (I = 0.0%, RR = 3.654; 95% CI: 1.711-7.801, -value = 0.0058) and flu-like syndrome were significantly more frequent adverse effects win vaccinated groups compared to the control group. Subgroup analysis also showed that vaccination leads to better OS duration in recurrent gliomas than primary gliomas, and in LGG than HGG (-value = 0). On the other hand, personalized vaccines showed better OS duration than non-personalized vaccines (-value = 0).
CONCLUSION
Vaccination is a type of immunotherapy which shows promising efficacy in treatment of malignant glioma patients in terms of OS, PFS and duration of survival. In addition, AFTV, peptide, and dendritic cell-based vaccines are among the most efficient vaccines for gliomas. Personalized vaccines also showed considerable efficacy for glioma treatments.
PubMed: 38707486
DOI: 10.3389/or.2024.1374513 -
Cell Communication & Adhesion 2015Dendritic cells (DCs) either boost the immune system (enhancing immunity) or dampen it (leading to tolerance). This dual effect explains their vital role in cancer... (Review)
Review
Dendritic cells (DCs) either boost the immune system (enhancing immunity) or dampen it (leading to tolerance). This dual effect explains their vital role in cancer development and progression. DCs have been tested as a predictor of outcomes for cancer progression. Eight studies evaluated tumour-infiltrating DCs (TIDCs) as a predictor for colorectal cancer (CRC) outcomes. The detection of TIDCs has not kept pace with the increased knowledge about the identification of DC subsets and their maturation status. For that reason, it is difficult to draw a conclusion about the performance of DCs as a predictor of outcome for CRC. In this review, we comprehensively examine the evidence for the in situ immune response due to DC infiltration, in predicting outcome in primary CRC and how such information may be incorporated into routine clinical assessment.
Topics: CD40 Antigens; Colorectal Neoplasms; Databases, Factual; Dendritic Cells; Humans; Prognosis; Survival Rate
PubMed: 26027852
DOI: 10.3109/15419061.2015.1036859 -
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 -
Biology of Blood and Marrow... Nov 2014Acute and chronic graft-versus-host disease (GVHD) remain major obstacles for successful allogeneic hematopoietic cell transplantation. Extracorporeal photopheresis... (Review)
Review
Acute and chronic graft-versus-host disease (GVHD) remain major obstacles for successful allogeneic hematopoietic cell transplantation. Extracorporeal photopheresis (ECP) modulates immune cells, such as alloreactive T cells and dendritic cells, and improves GVHD target organ function(s) in steroid-refractory GVHD patients. We performed a systematic review to evaluate the totality of evidence regarding the efficacy of ECP for treatment of acute and chronic steroid-refractory or steroid-dependent GVHD. Nine studies, including 1 randomized controlled trial, met inclusion criteria, with a total of 323 subjects. In pooled analyses, overall response rates (ORR) were .69 (95% confidence interval [CI], .34 to .95) and .64 (95% CI, .47 to .79) for acute and chronic GVHD, respectively. In acute GVHD organ-specific responses, ECP resulted in the highest ORR for cutaneous, with .84 (95% CI, .75 to .92), followed by gastrointestinal with .65 (95% CI, .52 to .78). Similar response rates were seen in chronic GVHD involving the skin and gastrointestinal tract. Conversely, ORR for chronic GVHD involving the lungs was only .15 (95% CI, 0 to .5). In chronic GVHD, grades 3 to 4 adverse events were reported at .38 (95% CI, .06 to .78). ECP-related mortality rates were extremely low. Rates of immunosuppression discontinuation were .55 (95% CI, .40 to .70) and .23 (95% CI, .07 to .44) for acute and chronic GVHD, respectively. In summary, albeit limited by numbers of available studies, pooled analyses of prospective studies demonstrate encouraging responses after ECP treatment in acute and chronic GVHD after failing corticosteroids. Further research efforts are needed to improve organ-specific responses.
Topics: Acute Disease; Adult; Child; Chronic Disease; Female; Graft vs Host Disease; Humans; Male; Middle Aged; Photopheresis; Prospective Studies; Young Adult
PubMed: 24867779
DOI: 10.1016/j.bbmt.2014.05.017