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Clinical Microbiology Reviews Apr 2017Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response... (Review)
Review
Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8 T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8 T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.
Topics: Cytokines; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; T-Lymphocytes
PubMed: 28179378
DOI: 10.1128/CMR.00090-16 -
International Journal of Molecular... Sep 2022Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of... (Review)
Review
Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.
Topics: Antineoplastic Agents, Immunological; Apoptosis Regulatory Proteins; B7-H1 Antigen; CTLA-4 Antigen; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Ligands; Liver Neoplasms; Lung Neoplasms; Myocarditis; Programmed Cell Death 1 Receptor
PubMed: 36142866
DOI: 10.3390/ijms231810948 -
Human Vaccines & Immunotherapeutics Dec 2024Cell-based therapeutic cancer vaccines use autologous patient-derived tumor cells, allogeneic cancer cell lines or autologous antigen presenting cells to mimic the... (Meta-Analysis)
Meta-Analysis
Cell-based therapeutic cancer vaccines use autologous patient-derived tumor cells, allogeneic cancer cell lines or autologous antigen presenting cells to mimic the natural immune process and stimulate an adaptive immune response against tumor antigens. The primary objective of this study is to perform a systematic literature review with an embedded meta-analysis of all published Phase 2 and 3 clinical trials of cell-based cancer vaccines in human subjects. The secondary objective of this study is to review trials demonstrating biological activity of cell-based cancer vaccines that could uncover additional hypotheses, which could be used in the design of future studies. We performed the systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The final review included 36 studies - 16 single-arm studies, and 20 controlled trials. Our systematic review of the existing literature revealed largely negative trials and our meta-analysis did not show evidence of clinical benefit from cell-based cancer-vaccines. However, as we looked beyond the stringent inclusion criteria of our systematic review, we identified significant examples of biological activity of cell-based cancer vaccines that are worth highlighting. In conclusion, the existing literature on cell-based cancer vaccines is highly variable in terms of cancer type, vaccine therapies and the clinical setting with no overall statistically significant clinical benefit, but there are individual successes that represent the promise of this approach. As cell-based vaccine technology continues to evolve, future studies can perhaps fulfill the potential that this exciting field of anti-cancer therapy holds.
Topics: Humans; Cancer Vaccines; Neoplasms; Antigens, Neoplasm; Adaptive Immunity
PubMed: 38544385
DOI: 10.1080/21645515.2024.2323256 -
Life (Basel, Switzerland) Aug 2021Antiphospholipid syndrome (APS) is an autoimmune disease characterized by autoreactive B and T cells against β2-glycoprotein I (B2GPI), with vascular thrombosis or... (Review)
Review
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by autoreactive B and T cells against β2-glycoprotein I (B2GPI), with vascular thrombosis or obstetrical complications. Dendritic cells (DCs) are crucial in the generation of autoimmunity. Here, we conducted a comprehensive systematic review on the relationship between DC and APS. We performed a literature search of PubMed as of 26 March 2021. A total of 33 articles were extracted. DCs are pivotal in inducing inflammatory responses and orchestrating adaptive immunity. DCs contribute to the local inflammation regarding vascular thrombosis or obstetrical complications. Both B2GPI and antiphospholipid antibodies (aPL) can promote antigen presentation by DCs and the generation or maintenance of autoimmunity. In addition, plasmacytoid DC activation is enhanced by aPL, thereby augmenting the inflammatory response. In line with these findings, DC modulation appears promising as a future treatment for APS. In conclusion, our review indicated the crucial role of DCs in the pathogenesis of APS. Deeper understanding of the complex relationship would help in developing new treatment strategies.
PubMed: 34440545
DOI: 10.3390/life11080801 -
Infection and Drug Resistance 2022Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main... (Review)
Review
Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main role in inflammatory cytokine responses. Similarly, alveolar macrophages produce IFN-β, IFN-α, TNF-α, IL-6, CXCL10, and CCL3, while alternatively activated macrophages differentiate at the late phase, and require IL-13 or IL-4 cytokines. Furthermore, activated NKT cells secrete IL-13 and IL-4 that cause lung epithelial, endothelial and fibroblasts to secrete eotaxin that enhances the recruitment of eosinophil to the lung. CD8 and CD4T cells infection by the virus decreases the IFN-γ and IL-2 production. Despite this, both are involved in terminating virus replication. CD8T cells produce a larger amount of IFN-γ than CD4T cells, and CD8T cells activated under type 2 conditions produce IL-4, down regulating CD8 expression, granzyme and IFN-γ production. Antiviral inhibitors inhibit biological functions of viral proteins. Some of them directly target the virus replication machinery and are effective at later stages of infection; while others inhibit F protein dependent fusion and syncytium formation. TMC353121 reduces inflammatory cytokines, TNF-α, IL-6, and IL-1β and chemokines, KC, IP-10, MCP and MIP1-α. EDP-938 inhibits viral nucleoprotein (N), while GRP-156784 blocks the activity of respiratory syncytial virus ribonucleic acid (RNA) polymerase. PC786 inhibits non-structural protein 1 (NS-1) gene, RANTES transcripts, virus-induced CCL5, IL-6, and mucin increase. In general, it is an immune reaction that is blamed for the disease severity and pathogenesis in respiratory syncytial virus infection. Anti-viral inhibitors not only inhibit viral entry and replication, but also may reduce inflammatory cytokines and chemokines. Many respiratory syncytial virus inhibitors are proposed; however, only palivizumab and ribavirin are approved for prophylaxis and treatment, respectively. Hence, this review is focused on immunity cell responses to respiratory syncytial virus and the role of antiviral inhibitors.
PubMed: 36540102
DOI: 10.2147/IDR.S387479 -
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 -
PloS One Apr 2011More than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
More than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC) have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis.
METHODOLOGY/PRINCIPAL FINDINGS
Data was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17) and RCC (12). Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD) amounted to a clinical benefit rate (CBR) of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403) revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5-44.1) and in RCC (OR 8.4, 95% CI 1.3-53.0). Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC) as well as access to draining lymph nodes on clinical outcome could be demonstrated.
CONCLUSIONS/SIGNIFICANCE
As a 'proof of principle' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines.
Topics: Cancer Vaccines; Carcinoma, Renal Cell; Dendritic Cells; Humans; Immunotherapy; Kidney Neoplasms; Male; Prostatic Neoplasms; Quality Control
PubMed: 21533099
DOI: 10.1371/journal.pone.0018801 -
Cytotherapy Aug 2018Dendritic cell (DC)-based immunotherapy has recently been reported frequently in the treatment of hepatocellular carcinoma (HCC); however, its efficacy remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND AIMS
Dendritic cell (DC)-based immunotherapy has recently been reported frequently in the treatment of hepatocellular carcinoma (HCC); however, its efficacy remains controversial. In this study, we aimed to evaluate the clinical efficacy of DC-based immunotherapy on HCC by conducting a systematic review and meta-analysis.
METHODS
PubMed, Cochrane Library, Embase and Web of Science were searched to identify clinical trials on DC-based immunotherapy for HCC published up to January 31, 2018. The articles were selected according to pre-established inclusion criteria and methodologic quality, and publication bias were evaluated.
RESULTS
A total of 1276 cases from 19 clinical trials were included. Compared with traditional treatment, further DC-based therapy enhanced the CD4 T/CD8 T ratio (standardized mean difference: 0.68, 95% confidence interval [CI] 0.46-0.89, P < 0.001); increased the 1-year, 18-month and 5-year progression-free survival (PFS) rate and the 1-year, 18-month and 2-year overall survival (OS) rate (relative risk > 1, P < 0.05), prolonged the median PFS time (median survival ratio [MSR]: 1.98, 95% CI: 1.60-2.46, P < 0.001) and median OS time (MSR: 1.72, 95% CI: 1.51-1.96, P < 0.001). Adverse reactions were mild.
CONCLUSIONS
DC-based therapy not only enhanced anti-tumor immunity, improved the survival rate and prolonged the survival time of HCC patients, but it was also safe. These findings will provide encouraging information for further development of DC-based immunotherapy as an adjuvant treatment for HCC. However, the results must be interpreted with caution because of the small study numbers, publication bias and the various of study designs, pre-treatment and therapeutic processes of DCs.
Topics: Adjuvants, Immunologic; Cancer Vaccines; Carcinoma, Hepatocellular; Combined Modality Therapy; Cytokine-Induced Killer Cells; Dendritic Cells; Humans; Immunotherapy, Adoptive; Liver Neoplasms; Progression-Free Survival; Survival Rate; Treatment Outcome
PubMed: 30072299
DOI: 10.1016/j.jcyt.2018.06.002 -
World Journal of Surgical Oncology Jul 2023Pancreatic follicular dendritic cell sarcoma (FDCS) is an exceptionally rare and low-to-moderate malignancy, with only seven reported cases to date. Clinical diagnosis...
INTRODUCTION
Pancreatic follicular dendritic cell sarcoma (FDCS) is an exceptionally rare and low-to-moderate malignancy, with only seven reported cases to date. Clinical diagnosis of FDCS is challenging due to the lack of distinct biological and radiographic features.
CASE PRESENTATION
A 67-year-old woman presented to the hospital with a 4-day history of severe abdominal pain. Imaging studies (CT and MRI) revealed a large cystic mass located at the tail of the pancreas, which was suspected to be myeloid sarcoma (MS) based on EUS and CT-guided pancreatic puncture. Postoperative pathology and immunohistochemistry confirmed the diagnosis of pancreatic FDCS. After the diagnosis was confirmed, the patient received postoperative chemotherapy with the CHOP regimen. At 11 months of follow-up, there was no evidence of recurrence. Seven published cases have been reviewed to comprehensively summarize the clinical characteristics, diagnosis, and treatment options of FDCS.
CONCLUSION
While imaging can be useful in detecting pancreatic FDCS, it should be interpreted with caution as it can be challenging to differentiate from other pancreatic tumors. Pathology and immunohistochemistry are considered the gold standard for diagnosis, with CD21, CD23, and CD35 being specific tumor cell markers. However, preoperative diagnosis of pancreatic FDCS remains difficult, and the pancreatic puncture may further increase the risk of misdiagnosis. The disease is highly prone to recurrence and metastasis, and surgery is the preferred method for both diagnosis and treatment of localized disease.
Topics: Female; Humans; Aged; Dendritic Cell Sarcoma, Follicular; Pancreas; Pancreatic Neoplasms; Abdominal Pain; Biomarkers, Tumor
PubMed: 37480085
DOI: 10.1186/s12957-023-03115-5 -
Frontiers in Physiology 2022Intensified training coupled with sufficient recovery is required to improve athletic performance. A stress-recovery imbalance can lead to negative states of...
Intensified training coupled with sufficient recovery is required to improve athletic performance. A stress-recovery imbalance can lead to negative states of overtraining. Hormonal alterations associated with intensified training, such as blunted cortisol, may impair the immune response. Cortisol promotes the maturation and migration of dendritic cells which subsequently stimulate the T cell response. However, there are currently no clear reliable biomarkers to highlight the overtraining syndrome. This systematic review and meta-analysis examined the effect of intensified training on immune cells. Outcomes from this could provide insight into whether these markers may be used as an indicator of negative states of overtraining. SPORTDiscus, PUBMED, Academic Search Complete, Scopus and Web of Science were searched until June 2022. Included articles reported on immune biomarkers relating to lymphocytes, dendritic cells, and cytokines before and after a period of intensified training, in humans and rodents, at rest and in response to exercise. 164 full texts were screened for eligibility. Across 57 eligible studies, 16 immune biomarkers were assessed. 7 were assessed at rest and in response to a bout of exercise, and 9 assessed at rest only. Included lymphocyte markers were CD3, CD4 and CD8 T cell count, NK cell count, NK Cytolytic activity, lymphocyte proliferation and CD4/CD8 ratio. Dendritic cell markers examined were CD80, CD86, and MHC II expression. Cytokines included IL-1β, IL-2, IL-10, TNF-α and IFN-γ. A period of intensified training significantly decreased resting total lymphocyte (0.57, 95% CI 0.30) and CD8 T cell counts (0.37, 95% CI 0.04), and unstimulated plasma IL-1β levels (0.63, 95% CI 0.17). Resting dendritic cell CD86 expression significantly increased ( 2.18, 95% CI 4.07). All other biomarkers remained unchanged. Although some biomarkers alter after a period of intensified training, definitive immune biomarkers are limited. Specifically, due to low study numbers, further investigation into the dendritic cell response in human models is required.
PubMed: 36439269
DOI: 10.3389/fphys.2022.998925