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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 -
Frontiers in Cardiovascular Medicine 2021Monocyte subsets in humans, i.e., classical (CM), intermediate (IM), and non-classical monocytes (NCM), are thought to differentially contribute to the pathogenesis of...
Monocyte subsets in humans, i.e., classical (CM), intermediate (IM), and non-classical monocytes (NCM), are thought to differentially contribute to the pathogenesis of atherosclerosis, the leading cause of cardiovascular disease (CVD). However, the association between monocyte subsets and cardiometabolic disorders and CVD is not well-understood. Thus, the aim of the current systematic review and meta-analysis was to evaluate recent findings from clinical studies that examined the association between the distribution of monocyte subsets in subjects with cardiometabolic disorders and CVD compared to healthy controls. Articles were systematically searched in CINAHL, PubMed and Cochrane Library. Articles were independently screened and selected by two reviewers. Studies that reported the percentage of each monocyte subset were included in the systematic review and meta-analysis. For the meta-analysis, a random-effects model was used to generate pooled standardized mean differences (SMD) between subjects with cardiometabolic disorders and healthy controls. A total of 1,693 articles were screened and 27 studies were selected for qualitative analyses. Among them, six studies were included in the meta-analysis. In total, sample size ranged from 22 to 135 and mean or median age from 22 to 70 years old. We found studies that reported higher percentage and number of IM and/or NCM in subjects with cardiometabolic disorders (9 out of 13 studies) and in subjects with CVD (11 out of 15 studies) compared to healthy controls. In the meta-analysis, the percentage of CM was lower [SMD = -1.21; 95% CI (-1.92, -0.50); = 0.0009; = 91%] and the percentage of IM [SMD = 0.56; 95% CI (0.23, 0.88); = 0.0008; = 65%] and NCM [SMD = 1.39; 95% CI (0.59, 2.19); = 0.0007; = 93%] were higher in subjects with cardiometabolic disorders compared to healthy controls. Individuals with cardiometabolic disorders and CVD may have a higher percentage of IM and NCM than healthy controls. Future studies are needed to evaluate the cause and biological significance of this potential altered distribution of monocyte subsets.
PubMed: 33681309
DOI: 10.3389/fcvm.2021.640124 -
Frontiers in Immunology 2023Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease... (Review)
Review
UNLABELLED
Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease progression remains to be deciphered. Biomarkers are needed to define pathophysiological processes of these disorders, who may increasingly co-exist in the elderly generations of the future, due to the rising prevalence in both and ameliorated treatment options with improved life expectancy in MS. The purpose of this review was to provide a systematic overview of inflammatory biomarkers, as measured in the cerebrospinal fluid (CSF), that are associated with clinical disease progression. International peer-reviewed literature was screened using the PubMed and Web of Science databases. Disease progression had to be measured using clinically validated tests representing baseline functional and/or cognitive status, the evolution of such clinical scores over time and/or the transitioning from one disease stage to a more severe stage. The quality of included studies was systematically evaluated using a set of questions for clinical, neurochemical and statistical characteristics of the study. A total of 84 papers were included (twenty-five for AD and 59 for MS). Elevated CSF levels of chitinase-3-like protein 1 (YKL-40) were associated with disease progression in both AD and MS. Osteopontin and monocyte chemoattractant protein-1 were more specifically related to disease progression in AD, whereas the same was true for interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic protein and IgG oligoclonal bands in MS. We observed a broad heterogeneity of studies with varying cohort characterization, non-disclosure of quality measures for neurochemical analyses and a lack of adequate longitudinal designs. Most of the retrieved biomarkers are related to innate immune system activity, which seems to be an important mediator of clinical disease progression in AD and MS. Overall study quality was limited and we have framed some recommendations for future biomarker research in this field.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42021264741.
Topics: Humans; Aged; Alzheimer Disease; Biomarkers; Disease Progression; Multiple Sclerosis
PubMed: 37520580
DOI: 10.3389/fimmu.2023.1162340 -
Cancers Aug 2021Inflammation plays a major role in cancer development and progression and has the potential to be used as a prognostic marker in cancer. Previous studies have attempted... (Review)
Review
Prognostic Utility of Platelet-Lymphocyte Ratio, Neutrophil-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio in Head and Neck Cancers: A Detailed PRISMA Compliant Systematic Review and Meta-Analysis.
Inflammation plays a major role in cancer development and progression and has the potential to be used as a prognostic marker in cancer. Previous studies have attempted to evaluate Platelet-to-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR) or monocyte-lymphocyte ratio (MLR) as indicators of inflammation/prognostic markers in cancer, but there is no common consensus on their application in clinical practice. The aim of this systematic review and meta-analysis is to (a) assess the prognostic efficacy of all three prognostic markers in comparison to each other and (b) investigate the prognostic potential of these three markers in HNC. The study followed PRISMA guidelines, with the literature being collated from multiple bibliographic databases. Preliminary and secondary screening were carried out using stringent inclusion/exclusion criteria. Meta-analysis was carried out on selected studies using CMA software and HR as the pooled effect size metric. A total of 49 studies were included in the study. The pooled HR values of PLR, NLR and MLR indicated that they were significantly correlated with poorer OS. The pooled effect estimates for PLR, NLR and MLR were 1.461 (95% CI 1.329-1.674), 1.639 (95% CI 1.429-1.880) and 1.002 (95% CI 0.720-1.396), respectively. Significant between-study heterogeneity was observed in the meta-analysis of all three. The results of this study suggest that PLR, NLR and MLR ratios can be powerful prognostic markers in head and neck cancers that can guide treatment. Further evidence from large-scale clinical studies on patient cohorts are required before they can be incorporated as a part of the clinical method. PROSPERO Registration ID: CRD42019121008.
PubMed: 34439320
DOI: 10.3390/cancers13164166 -
Scientific Reports Dec 2020Plant-based diets like vegetarian or vegan diets might influence circulating levels of inflammatory biomarkers, thereby reducing the risk of chronic diseases. This... (Comparative Study)
Comparative Study Meta-Analysis
Plant-based diets like vegetarian or vegan diets might influence circulating levels of inflammatory biomarkers, thereby reducing the risk of chronic diseases. This systematic review and meta-analysis aimed to investigate the associations of veganism and vegetarianism with circulating inflammatory biomarkers in comparison to omnivores. Literature search was conducted in Pubmed and EMBASE until April 2020 and mean differences of biomarkers were assessed for: C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1 receptor antagonist (IL-1 RA), tumor necrosis factor-alpha (TNF-ɑ), E-selectin, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), adiponectin, omentin-1 and resistin. Of initially identified 1073 publications, 21 cross-sectional studies met the inclusion criteria and were included in the systematic review and meta-analysis. Vegan diet was associated with lower levels of CRP compared to omnivores [mean difference - 0.54 mg/l, 95%-CI: - 0.79 to - 0.28, p < 0.0001]. This association was less pronounced in vegetarians [mean difference - 0.25 mg/l, 95%-CI: - 0.49 to 0.00, p = 0.05]. In patients with impaired kidney function, the association between vegetarian nutrition and CRP was much stronger with - 3.91 mg/l (95%-CI: - 5.23 to - 2.60; p < 0.0001). No substantial effects were observed for all other inflammatory biomarkers. Despite strong associations between CRP and a vegan or vegetarian diet were seen, further research is needed, as most inflammatory biomarkers were investigated only in single studies so far.
Topics: Biomarkers; C-Reactive Protein; Chronic Disease; Diet, Vegan; Diet, Vegetarian; Inflammation; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Interleukin-18; Interleukin-6
PubMed: 33303765
DOI: 10.1038/s41598-020-78426-8 -
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 -
Clinical and Experimental Medicine Sep 2023Immunotherapy is the main standard treatment for non-small cell lung cancer (NSCLC) patients. Immune suppressive cells in tumor microenvironment can counteract its... (Meta-Analysis)
Meta-Analysis Review
Immunotherapy is the main standard treatment for non-small cell lung cancer (NSCLC) patients. Immune suppressive cells in tumor microenvironment can counteract its efficacy. Myeloid-derived suppressor cells (MDSCs) include two major subsets: polymorphonuclear (PMN-MDSCs) and monocytic (M-MDSCs). Many studies explored the prognostic impact of these cell populations in NSCLC patients. The aim of this systematic review is to select studies for a meta-analysis, which compares prognosis between patients with high vs low circulating MDSC levels. We collected hazard ratios (HRs) and relative 95% confidence intervals (CIs) in terms of progression-free survival (PFS) or recurrence-free survival (RFS), and overall survival (OS). Among 139 studies retrieved from literature search, 14 eligible studies (905 NSCLC patients) met inclusion criteria. Low circulating MDSC levels favor a better PFS/RFS (HR = 1.84; 95% CI = 1.28-2.65) and OS (HR = 1.78; 95% CI = 1.29-2.46). The subgroup analysis based on MDSC subtypes (total-, PMN-, and M-MDSCs) obtained a statistical significance only for M-MDSCs, both in terms of PFS/RFS (HR = 2.67; 95% CI = 2.04-3.50) and OS (HR = 2.10; 95% CI = 1.61-2.75). NSCLC patients bearing high M-MDSC levels in peripheral blood experience a worse prognosis than those with low levels, both in terms of PFS/RFS and OS. This finding suggests that detecting and targeting this MDSC subset could help to improve NSCLC treatment efficacy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Myeloid-Derived Suppressor Cells; Prognosis; Lung Neoplasms; Proportional Hazards Models; Tumor Microenvironment
PubMed: 36401744
DOI: 10.1007/s10238-022-00946-6 -
Oncotarget May 2016Inflammation influences cancer development and progression, and a low lymphocyte to monocyte ratio (LMR) has been reported to be a poor prognostic indicator in several... (Meta-Analysis)
Meta-Analysis Review
Inflammation influences cancer development and progression, and a low lymphocyte to monocyte ratio (LMR) has been reported to be a poor prognostic indicator in several malignancies. Here we quantify the prognostic impact of this biomarker and assess its consistency in various cancers. Eligible studies were retrieved from PubMed, Embase and Web of Science databases. Overall survival (OS) was the primary outcome, cancer-specific survival (CSS), disease-free survival (DFS), recurrence-free survival (RFS), and progression-free survival (PFS) were secondary outcomes. Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Fifty-six studies comprising 20,248 patients were included in the analysis. Overall, decreased LMR was significantly associated with shorter OS in non-hematological malignancy (HR: 0.59, 95% CI: 0.53-0.66; P < 0.001) and hematological malignancy (HR: 0.44, 95% CI: 0.34-0.56; P < 0.001). Similar results were found in CSS, DFS, RFS and PFS. Moreover, low LMR was significantly associated with some clinicopathological characteristics that are indicative of poor prognosis and disease aggressiveness. By these results, we conclude that a decreased LMR implied poor prognosis in patients with cancer and could serve as a readily available and inexpensive biomarker for clinical decision.
Topics: Disease Progression; Disease-Free Survival; Humans; Inflammation; Lymphocytes; Monocytes; Neoplasms; Odds Ratio; Predictive Value of Tests; Risk Factors; Time Factors; Treatment Outcome
PubMed: 26942464
DOI: 10.18632/oncotarget.7876 -
Medicina (Kaunas, Lithuania) Sep 2022Background and objective: Among the broad variety of chemokines, monocyte chemoattractant protein-1 (MCP-1) is considered to be one of the most important chemokines.... (Meta-Analysis)
Meta-Analysis Review
Background and objective: Among the broad variety of chemokines, monocyte chemoattractant protein-1 (MCP-1) is considered to be one of the most important chemokines. Among others, MCP-1 activates monocytes and other immune cells highly involved in inflammation. In the present systematic review and meta-analysis, we evaluated the relationship between serum/plasma MCP-1 levels and the risk of obstructive sleep apnea (OSA) in adults as a disease related to inflammation. Materials and methods: Four databases were systematically investigated until 12 July 2022. We used the Review Manager 5.3 software (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) to extract and calculate the standardized mean difference (SMD) and its 95% confidence interval (CI) of plasma/serum levels of MCP-1 between adults with and without OSA. Results: Eight articles including eleven studies in adults were entered into the meta-analysis. The serum/plasma MCP-1 levels in adults with OSA were higher than that in the controls (SMD = 0.81; p = 0.0007) and as well as for adults with severe OSA compared to those with mild and moderate OSA (SMD = 0.42; p < 0.0001). The subgroup analysis showed that ethnicity was an effective factor in the pooled analysis of blood MCP-1 levels in adults with OSA compared to the controls (Asians: (p < 0.0001), mixed ethnicity: (p = 0.04), and Caucasians: (p = 0.89)). The meta-regression showed increasing serum/plasma MCP-1 levels in adults with OSA versus the controls, publication year, age of controls, body mass index (BMI) of controls, and sample size reduced, and also BMI and the apnea−hypopnea index of adults with OSA increased. Conclusions: The meta-analysis showed that compared to the controls, serum/plasma levels of MCP-1 in adults with OSA were significantly more, as well as adults with severe OSA having more serum/plasma MCP-1 levels compared to the adults with mild to moderate OSA. Therefore, MCP-1 can be used as a diagnostic and therapeutic factor in adults with OSA.
Topics: Adult; Chemokine CCL2; Humans; Inflammation; Monocytes; Sleep Apnea, Obstructive
PubMed: 36143943
DOI: 10.3390/medicina58091266 -
Frontiers in Psychiatry 2022Research on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in depression is still emerging and has...
BACKGROUND
Research on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in depression is still emerging and has increased 3-fold since the first meta-analysis. An updated meta-analysis with sufficient studies can provide more evidence for a potential relationship between NLR, PLR, MLR, and depression.
METHODS
We identified 18 studies from the PubMed, EMBASE, Cochrane library, and Web of Science databases. Meta-analyses were performed to generate pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) between patients with depression and controls. Sensitivity analysis, subgroup analysis, meta-regression, and publication bias were conducted.
RESULTS
A total of 18 studies including 2,264 depressed patients and 2,415 controls were included. Depressed patients had significantly higher NLR and PLR compared with controls (SMD = 0.33, 95% CI: 0.15-0.52, < 0.001 and SMD = 0.24, 95% CI: 0.02-0.46, < 0.05, respectively). MLR was slightly higher in depressed individuals compared to controls (SMD = 0.15, 95% CI: -0.26 to 0.55, > 0.05), despite the absence of significance. Sensitivity analysis removing one study responsible for heterogeneity showed a higher and significant effect (SMD = 0.32, 95% CI: 0.20-0.44) of MLR. Three subgroup analyses of NLR, PLR, MLR, and depression revealed obvious differences in the inflammatory ratios between depressed patients and controls in China and the matched age and gender subgroup. Individuals with post-stroke depression (PSD) had higher NLR and MLR values as compared to non-PSD patients (SMD = 0.51, 95% CI: 0.36-0.67, < 0.001 and SMD = 0.46, 95% CI: 0.12-0.79, < 0.01, respectively). Meta-regression analyses showed that male proportion in the case group influenced the heterogeneity among studies that measured NLR values ( < 0.05).
CONCLUSIONS
Higher inflammatory ratios, especially NLR, were significantly associated with an increased risk of depression. In the subgroup of China and matched age and gender, NLR, PLR, and MLR were all elevated in depressed patients vs. controls. Individuals with PSD had higher NLR and MLR values as compared to non-PSD patients. Gender differences may have an effect on NLR values in patients with depression.
PubMed: 35782448
DOI: 10.3389/fpsyt.2022.893097