-
International Journal of Molecular... Feb 2022Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed... (Review)
Review
Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.
Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Signal Transduction
PubMed: 35269752
DOI: 10.3390/ijms23052607 -
Frontiers in Immunology 2023Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival.
METHOD
Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356).
RESULTS
We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; = -2.00, = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; = -1.99, = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; = -3.53; = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; = -2.23; = 0.0256).
CONCLUSION
Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.
Topics: Humans; Standard of Care; Glioma; Brain Neoplasms; Progression-Free Survival; Immunotherapy
PubMed: 37483593
DOI: 10.3389/fimmu.2023.966696 -
Molecular Psychiatry Oct 2023Adolescence represents a critical period for brain and behavioural health and characterised by the onset of mood, psychotic and anxiety disorders. In rodents,...
Adolescence represents a critical period for brain and behavioural health and characterised by the onset of mood, psychotic and anxiety disorders. In rodents, neurogenesis is very active during adolescence, when is particularly vulnerable to stress. Whether stress-related neurogenesis changes influence adolescence onset of psychiatric symptoms remains largely unknown. A systematic review was conducted on studies investigating changes in hippocampal neurogenesis and neuroplasticity, hippocampal-dependent cognitive functions, and behaviour, occurring after adolescence stress exposure in mice both acutely (at post-natal days 21-65) and in adulthood. A total of 37 studies were identified in the literature. Seven studies showed reduced hippocampal cell proliferation, and out of those two reported increased depressive-like behaviours, in adolescent rodents exposed to stress. Three studies reported a reduction in the number of new-born neurons, which however were not associated with changes in cognition or behaviour. Sixteen studies showed acutely reduced hippocampal neuroplasticity, including pre- and post-synaptic plasticity markers, dendritic spine length and density, and long-term potentiation after stress exposure. Cognitive impairments and depressive-like behaviours were reported by 11 of the 16 studies. Among studies who looked at adolescence stress exposure effects into adulthood, seven showed that the negative effects of stress observed during adolescence on either cell proliferation or hippocampal neuroplasticity, cognitive deficits and depressive-like behaviour, had variable impact in adulthood. Treating adolescent mice with antidepressants, glutamate receptor inhibitors, glucocorticoid antagonists, or healthy diet enriched in omega-3 fatty acids and vitamin A, prevented or reversed those detrimental changes. Future research should investigate the translational value of these preclinical findings. Developing novel tools for measuring hippocampal neurogenesis in live humans, would allow assessing neurogenic changes following stress exposure, investigating relationships with psychiatric symptom onset, and identifying effects of therapeutic interventions.
Topics: Animals; Mice; Brain; Cognition; Hippocampus; Neurogenesis; Rodentia; Stress, Psychological
PubMed: 37612364
DOI: 10.1038/s41380-023-02229-2 -
Environmental Research May 2021Air pollution is a major public health threat. The present study is the first systematic review (SR) to determine the association of exposure to air pollution and... (Review)
Review
Air pollution is a major public health threat. The present study is the first systematic review (SR) to determine the association of exposure to air pollution and Multiple Sclerosis (MS) Progression. A Literature search was carried out using relevant keywords within several international databases. A comprehensive literature search was carried out systematically and yielded 24 eligible studies concerning the relationship of exposure to air pollution including criteria air pollutants such as particulate matter, NOx and SOx, CO, traffic noise, etc. and MS disease. The results of the included studies reveal that there was a significant relationship between exposure to air pollution and MS development and progression. Although the effect of air pollution in the pathogenesis of MS is notfully known, according to the results of the included studies exposure to polluted air can stimulate several mechanisms that act as risk factors for developing MS and for having disease relapses or neurological disability. The major potential mechanism is Dysimmune inflammatory responses subsequent oxidative stress (OS), which leads to neuroinflammation and breakdown of the normal balance between immunity and self-tolerance. Air pollutants induce and sustain chemical reactions that produce reactive oxygen species (ROSs) and nitrogen reactive species (RNSs) which can initiate inflammatory cascades via the redox-sensitive mitogen-activated protein kinase (MAPK) and NF-κB that recruit and activate neutrophils, monocytes, and dendritic cells that stimulate the adaptive immune responses such as Th1 and Th17 inflammatory responses. The uncontrolled inflammatory responses following these events cause cell death and the release of self-antigens capable of stimulating the production of auto-aggressive T-cells via enhancing antigen presentation and facilitate entry of these cells to the central nervous system. Thus, oxidative stress is the culprit in the systemic inflammation and immune imbalance development and progression, powerful risk factors in MS.
Topics: Air Pollutants; Air Pollution; Central Nervous System; Environmental Exposure; Humans; Multiple Sclerosis; Particulate Matter
PubMed: 33129851
DOI: 10.1016/j.envres.2020.110386 -
Advanced Drug Delivery Reviews Dec 2022Despite the advances in immunotherapy for cancer treatment, patients still obtain limited benefits, mostly owing to unrestrained tumour self-expansion and immune evasion... (Review)
Review
Despite the advances in immunotherapy for cancer treatment, patients still obtain limited benefits, mostly owing to unrestrained tumour self-expansion and immune evasion that exploits immunoregulatory mechanisms. Traditionally, myeloid cells have a dominantly immunosuppressive role. However, the complicated populations of the myeloid cells and their multilateral interactions with tumour/stromal/lymphoid cells and physical abnormalities in the tumour microenvironment (TME) determine their heterogeneous functions in tumour development and immune response. Tumour-associated myeloid cells (TAMCs) include monocytes, tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), and granulocytes. Single-cell profiling revealed heterogeneous TAMCs composition, sub-types, and transcriptomic signatures across 15 human cancer types. We systematically reviewed the biophysical heterogeneity of TAMC composition and pro/anti-tumoral and immuno-suppressive/stimulating properties of myeloid-derived microenvironments. We also summarised comprehensive clinical strategies to overcome resistance to immunotherapy from three dimensions: targeting TAMCs, reversing physical abnormalities, utilising nanomedicines, and finally, put forward futuristic perspectives for scientific and clinical research.
Topics: Humans; Immunotherapy; Tumor Microenvironment; Myeloid-Derived Suppressor Cells; Myeloid Cells; Neoplasms
PubMed: 36273512
DOI: 10.1016/j.addr.2022.114585 -
Journal of Reproductive Immunology Aug 2022The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for... (Review)
Review
The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for implantation. Histologically, the FT mucosa consists of three main cell types: secretory, ciliated and peg cells. In addition, several studies have reported the presence of immune cells. This systematic review aims to present a comprehensive analysis of the immune cell populations in the human FT, both in health and benign pathology, to promote a better understanding of tubal pathologies and their influence on infertility. A comprehensive literature search was conducted across five databases and augmented with manual citation chaining. Forty-two eligible studies were selected in accordance with PRISMA guidelines. Following screening, risk of bias assessments were conducted, data extracted and the findings presented thematically. T lymphocytes, predominantly CD8 T cells, represent the most abundant immune cell population within the healthy FT, with B lymphocytes, macrophages, NK cells and dendritic cells also localised to the tubal mucosa. There is evidence to suggest that lymphocyte and macrophage populations are susceptible to changes in the concentration of reproductive hormones. Tubal ectopic pregnancy, salpingitis, hydrosalpinx and endometriosis are all characterised by an increased population of macrophages in comparison to healthy FT. However, given the inconsistent evidence presented between studies, and the lack of studies examining all immune cell subtypes in tubal pathologies, only limited conclusions can be formulated on pathology-specific immune cell populations, and further research is required for validation.
Topics: CD8-Positive T-Lymphocytes; Fallopian Tubes; Female; Humans; Mucous Membrane; Pregnancy; Pregnancy, Tubal; Salpingitis
PubMed: 35644062
DOI: 10.1016/j.jri.2022.103646 -
Clinical and Experimental Allergy :... Mar 2023The aim of this study was to systematically review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this study was to systematically review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA).
DESIGN
A systematic review of the literature and meta-analysis were carried out within several databases. However, the risk of bias in the included articles was not evaluated.
DATA SOURCES
PubMed, Cochrane Database of Systematic Reviews, and Web of Science were used to search up to July 2022.
ELIGIBILITY CRITERIA
We included targeted and epigenome-wide association studies (EWASs) that assessed DNA methylome alterations in association with FA in adult or paediatric populations.
RESULTS
Among 366 publications, only 16 were retained, which were mainly focused on FA in children. Seven candidate gene-targeted studies found associations in Th1/Th2 imbalance (IL4, IL5, IL10, INFG, IL2 and IL12B genes), regulatory T cell function (FOXP3 gene), Toll-like receptors pathway (TLR2, CD14 genes) and digestive barrier integrity (FLG gene). Nine EWAS assessed the association with peanut allergy (n = 3), cow's milk allergy (n = 2) or various food allergens (n = 4). They highlighted 11 differentially methylated loci in at least two studies (RPS6KA2, CAMTA1, CTBP2, RYR2, TRAPPC9, DOCK1, GALNTL4, HDAC4, UMODL1, ZAK and TNS3 genes). Among them, CAMTA1 and RPS6KA2, and CTBP2 are involved in regulatory T cell function and Th2 cell differentiation, respectively. Gene-functional analysis revealed two enriched gene clusters involved in immune responses and protein phosphorylation. ChIP-X Enrichment Analysis 3 showed eight significant transcription factors (RXRA, ZBTB7A, ESR1, TCF3, MYOD1, CTCF, GATA3 and CBX2). Ingenuity Pathway Analysis identified canonical pathways involved, among other, in B cell development, pathogen-induced cytokine storm signalling pathway and dendritic cell maturation.
CONCLUSION
This review highlights the involvement of epigenomic alterations of loci in Th1/Th2 and regulatory T cell differentiation in both candidate gene studies and EWAS. These alterations provide a better insight into the mechanistic aspects in FA pathogenesis and may guide the development of epigenome-based biomarkers for FA.
Topics: Female; Animals; Cattle; Epigenome; Cell Line, Tumor; Transcription Factors; DNA-Binding Proteins; Food Hypersensitivity; Milk Hypersensitivity
PubMed: 36756739
DOI: 10.1111/cea.14277 -
Cytotherapy May 2024Acute myeloid leukemia (AML) is classified as a hematologic malignancy characterized by the proliferation of immature blood cells within the bone marrow (BM), resulting... (Review)
Review
BACKGROUND AIMS
Acute myeloid leukemia (AML) is classified as a hematologic malignancy characterized by the proliferation of immature blood cells within the bone marrow (BM), resulting in an aberrant and unregulated cellular growth. The primary therapeutic modalities for AML include chemotherapy and hematopoietic stem cell transplantation. However, it is important to note that these treatments are accompanied by important adverse effects and mortality rates. Therefore, the need for more effective treatment options seems necessary, and dendritic cell (DC) vaccine therapy can be one of these options. In this study, we aim to investigate the effectiveness of DC vaccination therapy for the management of AML.
METHODS
PubMed, Scopus, ProQuest, Web of Science, and Google Scholar databases were searched for this systematic review. The articles were evaluated based on the inclusion criteria of this study and initially compared in terms of titles or abstracts. Finally, the articles related to the topic of this review were obtained in full text. The complete remission and partial remission, survival, correlative immune assays, and health-related metrics were used to evaluate this cellular immunotherapy effectiveness. The quality of the studies was assessed independently using the Cochrane risk-of-bias tools. The compiled data were input into a standard Excel spreadsheet. Each domain was evaluated as having either a "low risk," "high risk," or "unclear risk" of bias.
RESULTS
Among the 3986 studies that were determined, a total of 11 correlated trials were selected for inclusion in this systematic review. DC vaccine therapy was effective in inducing complete and partial remission, and stabilization of the disease. Additionally, it was discovered that the treatment strengthened the immune system as seen by increased levels of CD4 and CD8 T cells, Th1 cytokines, WT1-specific T cells, and activated NK cells.
CONCLUSION
We conducted a systematic review that supports the use of DC vaccine therapy as an effective treatment for AML. The therapy demonstrated potentials in achieving remission, enhancing the immune system function, and increasing overall survival. However, more studies are required to improve the methods of preparing and delivering the DC vaccine, and to confirm its long-term safety and effectiveness.
Topics: Humans; Leukemia, Myeloid, Acute; Dendritic Cells; Cancer Vaccines; Vaccination; Immunotherapy
PubMed: 38483358
DOI: 10.1016/j.jcyt.2024.02.009 -
Expert Review of Vaccines Apr 2022Gliomas are major challenges of neuro-oncology due to high mortality. Clinical applications of dendritic cells (DCs) have yielded promising results in the clinical trial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gliomas are major challenges of neuro-oncology due to high mortality. Clinical applications of dendritic cells (DCs) have yielded promising results in the clinical trial pipelines over decades.
RESEARCH DESIGN
In this systematic review, we critically discuss the current status, future perspective, and challenges of DC therapy for gliomas . and summarize the study population, blinding, comparators, dosage, treatment regimens, efficacy, and safety issues of the clinical trials published on DC therapy for gliomas and also report the results of our meta-analysis on safety and immunological efficacy of DC therapy for gliomas.
RESULTS
The results of our meta-analysis indicated that the most frequent grade I/II adverse event (AE) reported in phase I or phase I/II trials was fatigue (∼16% and 24%). Moreover, in phase II trials, fatigue and cytopenia were the most common AEs (∼9% and 14%). Meanwhile, Grade III/IV AEs were rare . Moreover, our meta-analysis indicated ∼64% CD8+ T cells infiltration into tumor site after DC therapy and also ∼45% IFNγ increase.
CONCLUSIONS
DC therapy could serve as a potential immunotherapy for gliomas; however, limitations exist to draw certain conclusions due to diversity of the criteria applied to assess clinical response and limited data on patients' survival.
Topics: Brain Neoplasms; CD8-Positive T-Lymphocytes; Dendritic Cells; Glioma; Humans; Immunotherapy
PubMed: 35076331
DOI: 10.1080/14760584.2022.2027759 -
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