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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 -
Experimental & Molecular Medicine Mar 2024Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections,... (Review)
Review
Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections, malignancies, or medications. Characterized by the presence of hemophagocytic macrophages and a fulminant cytokine storm, sHLH/MAS leads to hyperferritinemia and multiorgan failure and rapidly progresses to death. The high mortality rate and the lack of specific treatments necessitate the development of a new drug. However, the complex and largely unknown immunopathologic mechanisms of sHLH/MAS, which involve dysfunction of various immune cells, diverse etiologies, and different clinical contexts make this effort challenging. This review introduces the terminology, diagnosis, and clinical features of sHLH/MAS. From a translational perspective, this review focuses on the immunopathological mechanisms linked to various etiologies, emphasizing potential drug targets, including key molecules and signaling pathways. We also discuss immunomodulatory biologics, existing drugs under clinical evaluation, and novel therapies in clinical trials. This systematic review aims to provide insights and highlight opportunities for the development of novel sHLH/MAS therapeutics.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Macrophages
PubMed: 38448692
DOI: 10.1038/s12276-024-01182-6 -
International Journal of Molecular... Nov 2022Autism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade... (Meta-Analysis)
Meta-Analysis Review
Activation of the Monocyte/Macrophage System and Abnormal Blood Levels of Lymphocyte Subpopulations in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.
Autism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade inflammation may be involved in the pathophysiology of this condition. However, studies investigating peripheral blood levels of immune cells, and/or of immune cell activation markers such as neopterin are lacking and have provided mixed findings. We performed a systematic review and meta-analysis of studies comparing total and differential white blood cell (WBC) counts, blood levels of lymphocyte subpopulations and of neopterin between individuals with ASD and typically developing (TD) controls (PROSPERO registration number: CRD CRD42019146472). Online searches covered publications from 1 January 1994 until 1 March 2022. Out of 1170 publication records identified, 25 studies were finally included. Random-effects meta-analyses were carried out, and sensitivity analyses were performed to control for potential moderators. Results: Individuals with ASD showed a significantly higher WBC count (k = 10, g = 0.29, p = 0.001, I2 = 34%), significantly higher levels of neutrophils (k = 6, g = 0.29, p = 0.005, I2 = 31%), monocytes (k = 11, g = 0.35, p < 0.001, I2 = 54%), NK cells (k = 7, g = 0.36, p = 0.037, I2 = 67%), Tc cells (k = 4, g = 0.73, p = 0.021, I2 = 82%), and a significantly lower Th/Tc cells ratio (k = 3, g = −0.42, p = 0.008, I2 = 0%), compared to TD controls. Subjects with ASD were also characterized by a significantly higher neutrophil-to-lymphocyte ratio (NLR) (k = 4, g = 0.69, p = 0.040, I2 = 90%), and significantly higher neopterin levels (k = 3, g = 1.16, p = 0.001, I2 = 97%) compared to TD controls. No significant differences were found with respect to the levels of lymphocytes, B cells, Th cells, Treg cells, and Th17 cells. Sensitivity analysis suggested that the findings for monocyte and neutrophil levels were robust, and independent of other factors, such as medication status, diagnostic criteria applied, and/or the difference in age or sex between subjects with ASD and TD controls. Taken together, our findings suggest the existence of a chronically (and systemically) activated inflammatory response system in, at least, a subgroup of individuals with ASD. This might have not only diagnostic, but also, therapeutic implications. However, larger longitudinal studies including more homogeneous samples and laboratory assessment methods and recording potential confounding factors such as body mass index, or the presence of comorbid psychiatric and/or medical conditions are urgently needed to confirm the findings.
Topics: Humans; Monocytes; Autism Spectrum Disorder; Neopterin; Leukocytes; Lymphocyte Subsets; Th17 Cells; Macrophages
PubMed: 36430805
DOI: 10.3390/ijms232214329 -
Frontiers in Veterinary Science 2022Studies on intracranial aneurysms (IAs) using animal models have evolved for decades. This study aimed to analyze major contributors and trends in IA-related animal...
INTRODUCTION
Studies on intracranial aneurysms (IAs) using animal models have evolved for decades. This study aimed to analyze major contributors and trends in IA-related animal research using bibliometric analysis.
METHODS
IA-related animal studies were retrieved from the Web of Science database. Microsoft Excel 2010, GraphPad Prism 6, VOSviewer, and CiteSpace were used to collect and analyze the characteristics of this field.
RESULTS
A total of 273 publications were retrieved. All publications were published between 1976 and 2021, and the peak publication year is 2019. Rat model were used in most of the publications, followed by mice and rabbits. Japan (35.5%), the United States (30.0%), and China (20.1%) were the top three most prolific countries. Although China ranks third in the number of publications, it still lacks high-quality articles and influential institutions. was the most prolific journal that accepted publications related to IA research using animal models. has the highest impact factor with IA-related animal studies. Hashimoto N contributed the largest number of articles. Meng hui journal published the first and second highest cited publications. The keywords "subarachnoid hemorrhage," "macrophage," "rupture," "mice," "elastase," "gene," "protein," "proliferation," and "risk factors" might be a new trend for studying IA-related animal research.
CONCLUSIONS
Japan and the Unites States contributed the most to IA-related animal studies, in terms of both researchers and institutions. Although China ranks third in terms of the number of publications, it should strengthen the quality of its publications. Researchers should pay attention to the latest progress of , and for their high-quality IA-related animal studies. Using animal IA models, especially mice, to investigate the molecular mechanisms of IA may be the frontier topic now and in future.
PubMed: 36467643
DOI: 10.3389/fvets.2022.1027453 -
Frontiers in Immunology 2022Glioblastoma (GBM) is the most common malignant brain tumor in adults, and immunotherapies and genetic therapies for GBM have evolved dramatically over the past decade,... (Review)
Review
Glioblastoma (GBM) is the most common malignant brain tumor in adults, and immunotherapies and genetic therapies for GBM have evolved dramatically over the past decade, but GBM therapy is still facing a dilemma due to the high recurrence rate. The inflammatory microenvironment is a general signature of tumors that accelerates epigenetic changes in GBM and helps tumors avoid immunological surveillance. GBM tumor cells and glioma-associated microglia/macrophages are the primary contributors to the inflammatory condition, meanwhile the modification of epigenetic events including DNA methylation, non-coding RNAs, and histone methylation and deacetylases involved in this pathological process of GBM, finally result in exacerbating the proliferation, invasion, and migration of GBM. On the other hand, histone deacetylase inhibitors, DNA methyltransferases inhibitors, and RNA interference could reverse the inflammatory landscapes and inhibit GBM growth and invasion. Here, we systematically review the inflammatory-associated epigenetic changes and regulations in the microenvironment of GBM, aiming to provide a comprehensive epigenetic profile underlying the recognition of inflammation in GBM.
Topics: Brain Neoplasms; Epigenesis, Genetic; Glioblastoma; Humans; Inflammation; Tumor Microenvironment
PubMed: 35572545
DOI: 10.3389/fimmu.2022.869307 -
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 -
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