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Oral Oncology Dec 2022Head and neck squamous cell carcinoma (HNSCC) is an immunogenic cancer type, and tumor associated macrophages (TAMs) are a major component of the tumor microenvironment... (Meta-Analysis)
Meta-Analysis Review
Head and neck squamous cell carcinoma (HNSCC) is an immunogenic cancer type, and tumor associated macrophages (TAMs) are a major component of the tumor microenvironment (TME). In this systematic review and meta-analysis, studies assessing tumor infiltration with CD68+, iNOS+, HLA-DR+, CD11b+, CD163+, CD206+, and CD204+TAMs were included, and correlation to survival hazard was studied. A low number of CD68+TAMs correlated to better overall survival (OS) in multivariate analysis (HR 1.36 95 %CI (1.07-1.72) P = .01). CD68+TAMs did not correlate to disease free survival (DFS), disease specific survival (DSS), progression free survival (PFS), or recurrence free survival (RFS). A low number of CD163+TAMs correlated to better OS in uni- and multivariate analysis (resp. HR 2.65 95 %CI (1.57-4.46) P = .01 and HR 2.42 95 %CI (1.72-3.41) P < .001). A low number of CD163+TAMs also correlated to better DFS and PFS, whereas a low number of CD204+TAMs only correlated to PFS. While IHC analysis of pan macrophage marker CD68 and M2-like marker CD163 both show prognostic utility in OS, CD163 is a stronger prognosticator, as indicated by multivariate meta-analysis. CD163+TAMs also correlate to DFS and PFS; outcomes that are more relevant to patients, thus showing promising results for future clinical implementation.
Topics: Humans; Prognosis; Squamous Cell Carcinoma of Head and Neck; Tumor-Associated Macrophages; Antigens, Differentiation, Myelomonocytic; Tumor Microenvironment; Head and Neck Neoplasms
PubMed: 36335818
DOI: 10.1016/j.oraloncology.2022.106227 -
RMD Open Jul 2023The objective of this systematic review was to provide an overview of current developments and potentially available therapeutic options for spondyloarthritis (SpA) in...
The 2023 pipeline of disease-modifying antirheumatic drugs (DMARDs) in clinical development for spondyloarthritis (including psoriatic arthritis): a systematic review of trials.
OBJECTIVES
The objective of this systematic review was to provide an overview of current developments and potentially available therapeutic options for spondyloarthritis (SpA) in the coming years.
METHODS
We conducted a systematic review of 17 national and international clinical trial databases for all disease-modifying antirheumatic drugs (DMARDs) for SpA that are already marketed, in clinical development or withdrawn. The search was performed on February 2023 with the keywords "spondyloarthritis", "ankylosing spondylitis" and "psoriatic arthritis". For each molecule, we only considered the study at the most advanced stage of clinical development.
RESULTS
Concerning axial SpA (axSpA), a total of 44 DMARDs were identified: 6 conventional synthetic DMARDs (csDMARDs), 27 biological DMARDs (bDMARDs) and 11 targeted synthetic DMARDs (tsDMARDs). Among the 18 targeted treatments (b+tsDMARDs) in current development, corresponding trials reached phase I (n=1), II (n=10) and III (n=7). Ten molecules are IL-17 inhibitors, two Janus kinase (JAK) inhibitors and two granulocyte-macrophage colony-stimulating factor inhibitors; four have another mode of action. Concerning psoriatic arthritis (PsA), 44 DMARDs were identified: 5 csDMARDs, 27 bDMARDs and 12 tsDMARDs. Among the 15 molecules in current development, corresponding trials reached phase II (n=8) and III (n=7). Six molecules are JAK inhibitors, six IL-17 inhibitors and one an IL-23 inhibitor; two have another mode of action.
CONCLUSION
This systematic review identified 18 and 15 molecules in clinical development for axSpA and PsA, respectively, which suggests a strengthening of the therapeutic arsenal in the coming years. However, with so many DMARDs but low target diversity, we will need to develop strategies or biomarkers to help clinicians make informed treatment decisions.
Topics: Humans; Arthritis, Psoriatic; Antirheumatic Agents; Interleukin-17; Spondylarthritis; Spondylitis, Ankylosing; Janus Kinase Inhibitors
PubMed: 37507210
DOI: 10.1136/rmdopen-2023-003279 -
Cureus Jun 2022Erdheim Chester disease (ECD) is a type of histiocytosis characterized by a variable clinical presentation. The treatment of ECD is complex and mainly unknown. We aim to... (Review)
Review
Erdheim Chester disease (ECD) is a type of histiocytosis characterized by a variable clinical presentation. The treatment of ECD is complex and mainly unknown. We aim to conduct a literature review of the treatment of ECD and consolidate the knowledge about the most recent and updated treatment for ECD. To conduct the systematic review, we used the preferred reporting items for systematic reviews and meta-analysis (PRISMA) protocol. To analyze the bias, we used the Cochrane collaboration risk-of-bias tool to assess the bias. We included observational studies and clinical trials on humans, which were written in English. Papers not fulfilling the objective of our study were excluded. Overall, the drug showed efficacy in the clinical trials, showing prolonged improvement and high rates of response rate. Overall, the drug was not well tolerated, and patients had a long list of side effects. Nevertheless, the drug seems to be a good option for second-line treatment for patients with ECD and BRAFV600 mutation.
PubMed: 35844342
DOI: 10.7759/cureus.25935 -
Arthritis Research & Therapy Apr 2021Osteoarthritis (OA) has long been regarded as a disease of cartilage degeneration, whereas mounting evidence implies that low-grade inflammation contributes to OA. Among... (Review)
Review
OBJECTIVE
Osteoarthritis (OA) has long been regarded as a disease of cartilage degeneration, whereas mounting evidence implies that low-grade inflammation contributes to OA. Among inflammatory cells involved, macrophages play a crucial role and are mediated by the local microenvironment to exhibit different phenotypes and polarization states. Therefore, we conducted a systematic review to uncover the phenotypic alterations of macrophages during OA and summarized the potential therapeutic interventions via modulating macrophages.
METHODS
A systematic review of multiple databases (PubMed, Web of Science, ScienceDirect, Medline) was performed up to February 29, 2020. Included articles were discussed and evaluated by two independent reviewers. Relevant information was analyzed with a standardized and well-designed template.
RESULTS
A total of 28 studies were included. Results were subcategorized into two sections depending on sources from human tissue/cell-based studies (12 studies) and animal experiments (16 studies). The overall observation indicated that M1 macrophages elevated in both synovium and circulation during OA development, along with lower numbers of M2 macrophages. The detailed alterations of macrophages in both synovium and circulation were listed and analyzed. Furthermore, interventions against OA via regulating macrophages in animal models were highlighted.
CONCLUSION
This study emphasized the importance of the phenotypic alterations of macrophages in OA development. The classical phenotypic subcategory of M1 and M2 macrophages was questionable due to controversial and conflicting results. Therefore, further efforts are needed to categorize macrophages in an exhaustive manner and to use advanced technologies to identify the individual roles of each subtype of macrophages in OA.
Topics: Animals; Humans; Inflammation; Macrophages; Osteoarthritis; Phenotype; Synovial Membrane
PubMed: 33838669
DOI: 10.1186/s13075-021-02457-3 -
Diagnostics (Basel, Switzerland) Aug 2022Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed... (Review)
Review
Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed complex interactions between infectious agents and hosts that result in heterogeneous manifestations of sepsis. Sepsis can cause immunosuppression and increase the expression of checkpoint inhibitor molecules, including programmed death protein (PD-1) and programmed death ligand 1 (PD-L1), and thus PD-1 and PD-L1 are thought to be useful as diagnostic and prognostic tools for sepsis. PD-1 is an inhibitor of both adaptive and innate immune responses, and is expressed on activated T lymphocytes, natural killer (NK) cells, B lymphocytes, macrophages, dendritic cells (DCs), and monocytes, whereas PD-L1 is expressed on macrophages, some activated T and B cells, and mesenchymal stem cells as well as various non-hematopoietic cells. This systematic review aims to assess the PD-1 and PD-L1 protein expression levels and concentrations in septic and other infectious patients.
PubMed: 36010357
DOI: 10.3390/diagnostics12082004 -
Stem Cells International 2021Bone regeneration is a complex and well-coordinated process that involves crosstalk between immune cells and resident cells in the injury site. Transplantation of... (Review)
Review
Bone regeneration is a complex and well-coordinated process that involves crosstalk between immune cells and resident cells in the injury site. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy to enhance bone regeneration. Growing evidence suggests that macrophages have a significant impact on osteogenesis during bone regeneration. However, the precise mechanisms by which macrophage subtypes influence bone regeneration and how MSCs communicate with macrophages have not yet been fully elucidated. In this systematic literature review, we gathered evidence regarding the crosstalk between MSCs and macrophages during bone regeneration. According to the PRISMA protocol, we extracted literature from PubMed and Embase databases by using "mesenchymal stem cells" and "macrophages" and "bone regeneration" as keywords. Thirty-three studies were selected for this review. MSCs isolated from both bone marrow and adipose tissue and both primary macrophages and macrophage cell lines were used in the selected studies. In conclusion, anti-inflammatory macrophages (M2) have significantly more potential to strengthen bone regeneration compared with naïve (M0) and classically activated macrophages (M1). Transplantation of MSCs induced M1-to-M2 transition and transformed the skeletal microenvironment to facilitate bone regeneration in bone fracture and bone defect models. This review highlights the complexity between MSCs and macrophages, providing more insight into the polarized macrophage behavior in this evolving field of osteoimmunology. The results may serve as a useful reference for definite success in MSC-based therapy based on the critical interaction with macrophages.
PubMed: 34221025
DOI: 10.1155/2021/8835156 -
Frontiers in Immunology 2022To review the role of inflammation in the occurrence and development of benign prostatic hyperplasia (BPH), we searched PubMed for the latest published articles up to... (Review)
Review
To review the role of inflammation in the occurrence and development of benign prostatic hyperplasia (BPH), we searched PubMed for the latest published articles up to February 2021 using the following key words: "benign prostatic hyperplasia", "inflammation", "pathogenesis" and "disease development". Articles were obtained and reviewed to provide a systematic review of the current progress of the role of inflammation in the pathogenesis and progression of BPH. Inflammation contributes to the initiation and maintenance of unregulated cell proliferation and is closely related to the occurrence and development of BPH. Its action pathways include tissue damage and subsequent chronic healing, autoimmunity, and coaction with androgens. During the progression of inflammation, macrophages, interleukin-8 (IL-8), interleukin-1 (IL-1) and other inflammatory-related substances aggregate locally and cause BPH through various biochemical pathways. At the same time, BPH can also counteract inflammation to expand its scope and aggravate the situation. Inflammation can independently affect the development of BPH in a variety of ways, and it can also interact with androgens. In the course of treatment, early intervention in the occurrence and development of inflammation in prostate tissue can slow down the progression of BPH. The combination of standard therapies and anti-inflammatory measures may provide valuable new ideas for the treatment of BPH.
Topics: Aging; Androgens; Anti-Inflammatory Agents; Humans; Inflammation; Male; Prostatic Hyperplasia
PubMed: 35386711
DOI: 10.3389/fimmu.2022.842008 -
Virology Journal Nov 2023The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation on the basis of preclinical trial reports.
METHODS
Publicly available databases (PubMed, Embase, Medline, Web of Science and Cochrane Library.) and register (Clinicaltrials.gov) were searched to collect treatment outcomes of oncolytic virotherapies (including herpes simplex virus type 1 (HSV), coxsackievirus A21 (CVA21), adenovirus, poxvirus and reovirus) for advanced/unresectable melanoma. Comparisons of treatment response, adverse events (AEs) and survival analyses for different virotherapies were performed by R software based on the extracted data from eligible studies.
RESULTS
Finally, thirty-four eligible studies were analysed and HSV virotherapy had the highest average complete response (CR, 24.8%) and HSV had a slightly higher average overall response rate (ORR) than CVA21 (43.8% vs 42.6%). In the pooled results of comparing talimogene laherparepve (T-VEC) with or without GM-CSF/ICIs (immune checkpoint inhibitors) to GM-CSF/ICIs monotherapy suggested virotherapy was more efficient in subgroups CR (RR = 1.80, 95% CI [1.30; 2.51], P < 0.01), ORR (RR = 1.17, 95% CI [1.02; 1.34], P < 0.05), and DCR (RR = 1.27, 95% CI [1.15; 1.40], P < 0.01). In patients treated with T-VEC+ICIs, 2-year overall survival (12.1 ± 6.9 months) and progression-free survival (9.9 ± 6.9) were significantly longer than those treated with T-VEC alone. Furthermore, we found that AEs occurred frequently in virotherapy but decreased in a large cohort of enrolled patients, some of which, such as abdominal distension/pain, injection site pain and pruritus, were found to be positively associated with disease progression in patients treated with T-VEC monotherapy.
CONCLUSION
Given the relative safety and tolerability of oncolytic viruses, and the lack of reports of dose-limiting-dependent toxicities, more patients treated with T-VEC with or without ICIs should be added to future assessment analyses. There is still a long way to go before it can be used as a first-line therapy for patients with advanced or unresectable melanoma.
Topics: Humans; Oncolytic Virotherapy; Granulocyte-Macrophage Colony-Stimulating Factor; Immunotherapy; Melanoma; Oncolytic Viruses; Pain
PubMed: 37919738
DOI: 10.1186/s12985-023-02220-x -
European Review For Medical and... Jul 2023Bisphosphonates, the most common anti-resorptive medications, are internalized by osteoclasts, where they inhibit the macrophage colony-stimulating factor (M-CSF)...
OBJECTIVE
Bisphosphonates, the most common anti-resorptive medications, are internalized by osteoclasts, where they inhibit the macrophage colony-stimulating factor (M-CSF) pathway, preventing their differentiation, inhibiting anchorage to the cell membrane, and inducing apoptosis. In patients undergoing oral bisphosphonate therapy, oral surgery involves a high risk of developing drug-related osteonecrosis of the jaws (BRONJ/MRONJ), among the possible complications.
MATERIALS AND METHODS
A systematic search was carried out on the PubMed, Scopus and Cochrane Library search engines, using the keywords "oral bisphosphonates AND tooth extraction", "third molar extraction AND oral bisphosphonates". In addition, we manually evaluated the articles included in references from other sources and an analysis of the Gray Literature was performed. A secondary outcome was to evaluate the assessment of pharmacological (antibiotics) use in the BRONJ/MRONJ management. The revision protocol followed the indications of the Cochrane Handbook, and was registered in the INPLASY database, while the drafting of the manuscript was based on PRISMA.
RESULTS
The results of the systematic review, after the study identification and selection process, included a total of 7 studies: 4 retrospective studies, 2 prospective studies and 1 case report. The main complication was represented by osteonecrosis of the jaws, which appears to be related to the duration of treatment with bisphosphonates; in addition, data regarding the anatomical location of post-extraction sites, the sex and age of patients, comorbidities and various systemic risk factors were extrapolated. The most frequent post-extraction complication in patients treated with oral bisphosphonates is osteonecrosis of the jaws, with a significant prevalence in the posterior region of the mandible. In some cases, delayed healing of the surgical wound was also found; moreover, the duration of exposure to oral bisphosphonates influences the onset of complications.
CONCLUSIONS
Ongoing studies continue to unravel the role of the oral environment response in alveolar bone homeostasis and how it might contribute to the induction of BRONJ/MRONJ. Approaching the problem from this perspective could provide new directions for the prevention of BRONJ/MRONJ and expand our understanding of the unique oral microenvironment.
Topics: Humans; Bone Density Conservation Agents; Prospective Studies; Retrospective Studies; Bisphosphonate-Associated Osteonecrosis of the Jaw; Diphosphonates; Osteonecrosis; Tooth Extraction
PubMed: 37458653
DOI: 10.26355/eurrev_202307_32996 -
Cytokine Feb 2023Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent deactivating properties on macrophages and T cells; and plays an important role in atherosclerotic... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent deactivating properties on macrophages and T cells; and plays an important role in atherosclerotic plaque maturation and rupture. A guanine (G) to adenine (A) substitution in the IL-10 gene at -1082 bp (rs1800896) has been associated with reduced in IL-10 production in vitro. Against this background, we tested the association of IL-10 -1082G/A with early or severe presentation of coronary artery disease (CAD) using a systematic review and updated meta-analysis of published association studies.
MATERIALS AND METHODS
Relevant studies were identified following a comprehensive online search on PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science databases and stratified into two subgroups based on mode of CAD presentation: early or severe and non-severe. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random effects employing a Z test.
RESULTS
A total of 24 studies were included for quantitative synthesis with a cumulative sample of 19,135 (11,143 cases / 7,992 controls). A significant association was derived for IL-10 -1082G/A and early or severe CAD via dominant, recessive, and allelic genetic model comparisons [OR 1.24 (95 % CI 1.02, 1.50), p = 0.03; OR 1.32 (95 % CI 1.03, 1.69), p = 0.03 and OR 1.18 (95 % CI 1.02, 1.36), p = 0.02 respectively]. In contrast, no significant association was seen for the pooled group or non-severe CAD subgroup (p = NS). Sensitivity analysis showed consistent results.
CONCLUSIONS
IL-10 -1082G/A appears to be associated with early or severe presentation of CAD. Further studies are warranted to confirm this association.
Topics: Humans; Coronary Artery Disease; Interleukin-10; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Gene Expression
PubMed: 36463660
DOI: 10.1016/j.cyto.2022.156103