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Strahlentherapie Und Onkologie : Organ... Dec 2023Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells,... (Review)
Review
OBJECTIVE
Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells, radiation therapy (RT) can alter TME composition. With this systematic review, we provide a better understanding on how RT can regulate macrophage characterization, namely the M1 antitumor and the M2 protumor polarization, with the aim of describing new effective RT models and exploration of the possibility of integrating radiation with other available therapies.
METHODS
A systematic search in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out in PubMed, Google Scholar, and Scopus. Articles from January 2000 to April 2020 which focus on the role of M1 and M2 macrophages in the response to RT were identified.
RESULTS
Of the 304 selected articles, 29 qualitative summary papers were included in our analysis (16 focusing on administration of RT and concomitant systemic molecules, and 13 reporting on RT alone). Based on dose intensity, irradiation was classified into low (low-dose irradiation, LDI; corresponding to less than 1 Gy), moderate (moderate-dose irradiation, MDI; between 1 and 10 Gy), and high (high-dose irradiation, HDI; greater than 10 Gy). While HDI seems to be responsible for induced angiogenesis and accelerated tumor growth through early M2-polarized TAM infiltration, MDI stimulates phagocytosis and local LDI may represent a valid treatment option for possible combination with cancer immunotherapeutic agents.
CONCLUSION
TAMs seem to have an ambivalent role on the efficacy of cancer treatment. Radiation therapy, which exerts its main antitumor activity via cell killing, can in turn interfere with TAM characterization through different modalities. The plasticity of TAMs makes them an attractive target for anticancer therapies and more research should be conducted to explore this potential therapeutic strategy.
Topics: Humans; Tumor-Associated Macrophages; Neoplasms; Macrophages; Tumor Microenvironment
PubMed: 37347290
DOI: 10.1007/s00066-023-02097-3 -
Head & Neck Feb 2023Several studies have reported the value of neutrophil-to-lymphocyte ratio (NLR) for the prognosis of hypopharyngeal cancer. However, contradictory findings have also... (Meta-Analysis)
Meta-Analysis Review
Several studies have reported the value of neutrophil-to-lymphocyte ratio (NLR) for the prognosis of hypopharyngeal cancer. However, contradictory findings have also been published. We aimed to clarify the effect of NLR on the prognosis of hypopharyngeal cancer through meta-analysis. Systematic search of PubMed and other database with study selection and data extraction. The combined hazard ratio (HR) and 95% confidence intervals (CI) were calculated using STATA, applying either a fixed-effects or random-effects model. Meta-regression, subgroup analysis, and sensitivity analysis were used to analyze sources of heterogeneity. Publication bias were also assessed. This meta-analysis included 2232 patients with hypopharyngeal cancer from seven studies. The combined HR (OS, HR = 1.80, 95CI%, 1.14-2.82; PFS, HR = 1.88, 95CI%, 1.26-2.79) suggested that high NLR was associated with poor overall survival (OS) and progression-free survival (PFS). Pretreatment NLR can be used as an effective serological indicator to assess the prognosis of patients with hypopharyngeal cancer.
Topics: Humans; Hypopharyngeal Neoplasms; Lymphocyte Count; Lymphocytes; Neutrophils; Prognosis
PubMed: 36367335
DOI: 10.1002/hed.27246 -
Clinical Endocrinology Mar 2021Neutropenia, a low absolute neutrophil count (ANC), may be a sign of new-onset hyperthyroidism. The aim of this systematic review and meta-analysis was to provide the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Neutropenia, a low absolute neutrophil count (ANC), may be a sign of new-onset hyperthyroidism. The aim of this systematic review and meta-analysis was to provide the most reliable estimates of prevalence, degree and response to treatments of neutropenia in the pure hyperthyroidism setting.
METHODS
A comprehensive literature search was performed in PubMed and Scopus databases for retrieving articles in English and non-English languages reporting ANC values/neutropenic cases at presentation and after therapy in patients with hyperthyroidism. A proportion meta-analysis was performed with DerSimonian and Laird method (random-effects model). Pooled data were presented with 95% confidence intervals (95% CI) and displayed in a forest plot. I statistic index was used to quantify the heterogeneity among the studies. Sensitivity analyses for the prevalence of neutropenia and the mean of ANC in hyperthyroid patients were performed by excluding the studies without full details. Trim and fill analysis and Egger's linear regression test were carried out to evaluate the publication bias. A two-sided P-value of <.05 was regarded as significant for all analyses. The National Heart, Lung and Blood Institute Quality Assessment Tool was used to evaluate the quality of studies included.
RESULTS
The literature search yielded 1880 studies of which 13 studies were included for systematic review and meta-analysis. Results of the meta-analysis demonstrated that the prevalence of neutropenia in newly diagnosed and untreated patients with Graves' hyperthyroidism was 10% (CI 5%-19%, I 88.6%) and summary mean ANC value in neutropenic was 1.4 ± 0.3 × 10 /L. In all neutropenic patients under ATD therapy neutropenia resolved, thus without the worsening of the baseline ANC values or the development of agranulocytosis. The sensitivity analyses showed similar results as those of the main analyses. For all outcomes, the publication bias was not statistically significant or not calculable.
CONCLUSIONS
Graves' disease per se is associated with neutropenia in about 10% of cases. Neutropenia usually appears as a mild to moderate laboratory abnormality with no detectable consequences. Subnormal/mild neutropenia should not be regarded as a contraindication to use ATDs, and clinicians should know that treating hyperthyroidism they have a significant chance to normalize ANC too.
Topics: Graves Disease; Humans; Hyperthyroidism; Neutropenia; Neutrophils; Prevalence
PubMed: 32799342
DOI: 10.1111/cen.14313 -
Obesity Reviews : An Official Journal... Nov 2019Obesity is associated with the production of inflammatory cytokines that are implicated in insulin resistance (IR), and if not addressed, can lead to type 2 diabetes...
Obesity is associated with the production of inflammatory cytokines that are implicated in insulin resistance (IR), and if not addressed, can lead to type 2 diabetes (T2D). The role of the immune system in skeletal muscle (SM) inflammation and insulin sensitivity is not yet well characterized. As SM IR is an important determinant of glycaemia, it is critical that the muscle-immune phenotype is mapped to help design interventions to target T2D. This systematic review synthesized the evidence for SM macrophage content and phenotype in humans and murine models of obesity, and the association of muscle macrophage content and phenotype with IR. Results were synthesized narratively, as we were unable to conduct a meta-analysis. We included 28 studies (n=10 human, n=18 murine), and all studies detected macrophage markers in SM. Macrophage content was positively associated with IR. In humans and mice, there was variability in muscle macrophage content and phenotype in obesity. Overall certainty in the evidence was low due to heterogeneity in detection methods and incompleteness of data reporting. Macrophages are detected in human and murine SM in obesity and a positive association between macrophage content and IR is noted; however, the standardization of markers, detection methods, and reporting of study details is warranted to accurately characterize macrophages and improve the potential for creating specific and targeted immune-based therapies in obesity.
Topics: Animals; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucose Clamp Technique; Humans; Inflammation; Insulin Resistance; Macrophage Activation; Macrophages; Mice; Muscle, Skeletal; Obesity
PubMed: 31410961
DOI: 10.1111/obr.12922 -
Frontiers in Immunology 2023Rheumatoid arthritis (RA) is an autoimmune disease that currently has an unknown cause and pathogenesis, and is associated with many complications and a high disability...
Rheumatoid arthritis (RA) is an autoimmune disease that currently has an unknown cause and pathogenesis, and is associated with many complications and a high disability rate. The neutrophil extracellular trap network (NETs) is a newly discovered mechanism that allows neutrophils to capture and kill pathogens. Multiple studies in recent years have highlighted its relevance to the progression of rheumatoid arthritis. Despite the growing number of studies indicating the crucial role of NETs in RA, there has been no bibliometric review of research hotspots and trends in this area. In this study, we retrieved articles related to NETs in RA from the Web of Science Core Collection (WoSCC) database from 1985 to 2023 and used visualization tools such as Citespace, VOSviewer, Tableau Public, and Microsoft Office Excel 2021 to analyze the data. After screening, we included a total of 416 publications involving 2,334 researchers from 1,357 institutions in 167 countries/regions, with relevant articles published in 219 journals. The U.S., China, and Germany are the top 3 countries/regions with 124, 57, and 37 publications respectively. Mariana J. Kaplan is the most published author, and journals such as Frontiers in Immunology and International Journal of Molecular Sciences have had a significant impact on research in this field. The clinical application of PAD enzymes and their inhibitors, and the drug development of NETs as therapeutic targets for RA is a trend for future research. Our study provides a comprehensive bibliometric analysis and summary of NETs in RA publications, which will aid researchers in conducting further scientific research.
Topics: Humans; Extracellular Traps; Arthritis, Rheumatoid; Autoimmune Diseases; Neutrophils; Bibliometrics
PubMed: 37680637
DOI: 10.3389/fimmu.2023.1205445 -
BioMed Research International 2022In light of the growing emphasis on classifying stroke patients for different levels of monitoring intensity and emergency treatments, we conducted a systematic review... (Meta-Analysis)
Meta-Analysis Review
In light of the growing emphasis on classifying stroke patients for different levels of monitoring intensity and emergency treatments, we conducted a systematic review of a wide range of clinical studies, according to the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, with no restrictions on the language or publication date, to analyze the potential of the neutrophil-to-lymphocyte ratio (NLR) as an early neurological deterioration (END) risk predictor. A comprehensive search was carried out in PubMed, Scopus, and Web of Science databases from the inception to March 13, 2022. Nine articles were included in our study. Stroke patients with END had significantly higher NLR levels than the those without END (SMD = 0.73; CI 95% = 0.42-1.05, value < 0.001). In the subgroup analysis, according to ethnicity, East Asian patients with END had elevated levels of NLR compared to those without END (SMD = 0.79; CI 95% = 0.52-1.06, value < 0.001). However, the difference in the Caucasian group was not significant (SMD = 0.60; CI 95% = -0.50-1.70, value = 0.28). In the subgroup analysis according to the type of stroke, the NLR levels in patients with hemorrhagic stroke who developed END were similar to those without END (SMD = 0.84, CI 95% = -0.10-1.77, value = 0.07). Vice versa, in the ischemic stroke group, patients with END had elevated levels of NLR compared to those without END (SMD = 0.67, CI 95% = 0.38-0.96, value < 0.001). NLR is a unique inflammatory biomarker whose increase in END suggests an immune system dysfunction in the pathogenesis of the disease.
Topics: Biomarkers; Humans; Lymphocytes; Neutrophils; Stroke
PubMed: 36033552
DOI: 10.1155/2022/8656864 -
Antioxidants (Basel, Switzerland) Aug 2022Genetic association studies have discovered the intergenic region as a strong susceptibility locus for multiple autoimmune disorders, with the missense mutation... (Review)
Review
Genetic association studies have discovered the intergenic region as a strong susceptibility locus for multiple autoimmune disorders, with the missense mutation rs201802880 as the causal polymorphism. In this work, we aimed to perform a comprehensive meta-analysis of the association of the locus with various autoimmune diseases and to provide a systemic review on potential mechanisms underlying the effect of the causal risk variants. The frequencies of the two most extensively investigated polymorphisms within the locus, rs117026326 and rs201802880, vary remarkably across the world, with the highest frequencies in East Asian populations. Meta-analysis showed that the locus is significantly associated with primary Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, and neuromyelitis optica spectrum disorder. The causal rs201802880 polymorphism leads to an amino acid substitution of p.Arg90His in the p47phox subunit of the phagocyte NADPH oxidase. The autoimmune disease risk His90 variant results in a reduced ROS production in phagocytes. Clinical and experimental evidence shows that the hypoactive His90 variant might contribute to the development of autoimmune disorders via multiple mechanisms, including impairing the clearance of apoptotic cells, regulating the mitochondria ROS-associated formation of neutrophil extracellular traps, promoting the activation and differentiation of autoreactive T cells, and enhancing type I IFN responses. In conclusion, the identification of the association of with autoimmune disorders demonstrates that ROS is an essential regulator of immune tolerance and autoimmunity mediated disease manifestations.
PubMed: 36009308
DOI: 10.3390/antiox11081589 -
Langenbeck's Archives of Surgery Feb 2023Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR),... (Meta-Analysis)
Meta-Analysis Review
Prognostic role of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte, and lymphocyte-to-monocyte ratio in operated rectal cancer patients: systematic review and meta-analysis.
BACKGROUND
Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been proposed as useful prognostic indexes in cancer patients. However, their role in rectal cancer is controversial.
METHODS
A comprehensive literature review was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, and the Cochrane Database of Systematic Reviews through May 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Quality was appraised with the Methodological Index for Non-Randomized Studies (MINORS) tool. Aim of the study was to summarize available literature on PLR, NLR, and LMR in patients with rectal cancer undergoing resection.
RESULTS
Forty-seven observational studies (14,205 patients) were included; there were 42 retrospective and 5 prospective cohort studies with an average MINORS score of 14.6 (range: 12-18). Worse overall survival was associated with high NLR (HR 1.81; 95%CI 1.52-2.15; p < 0.001), high PLR (HR 1.24; 95%CI 1.06-1.46; p = 0.009), and low LMR (HR 0.67; 95%CI 0.49-0.91; p = 0.01). High NLR and low LMR were also associated with disease-free-survival (HR 1.68; 95%CI 1.35-2.08; p < 0.001 and HR 0.71; 95%CI 0.58-0.87; p < 0.001, respectively).
CONCLUSIONS
NLR, PLR, and LMR are independent clinical predictors for overall survival in patients with rectal cancer treated with curative surgery. NLR and LMR are also good predictors for disease free survival. These biomarkers, which are readily available, appear optimal prognostic indexes and may help clinicians predict the prognosis of rectal cancer and develop individualized treatment strategies.
Topics: Humans; Prognosis; Neutrophils; Monocytes; Retrospective Studies; Prospective Studies; Lymphocytes; Biomarkers; Rectal Neoplasms
PubMed: 36781510
DOI: 10.1007/s00423-023-02786-8 -
Journal of Diabetes and Its... Apr 2022Diabetes mellitus is a state of chronic low-grade inflammation. Scavenger receptor CD163, expressed on monocyte/macrophage cells with anti-inflammatory functions, has... (Review)
Review
AIMS
Diabetes mellitus is a state of chronic low-grade inflammation. Scavenger receptor CD163, expressed on monocyte/macrophage cells with anti-inflammatory functions, has been observed in diabetes complications. This review aimed to systematically survey human studies published until 31st January 2022 for CD163 expression, in particular diabetes complications and additionally to investigate whether CD163 may be implicated as a biomarker of, and mediator in, the progression of diabetes complications.
METHODS
A systematic literature search undertaken in Scopus, Embase and Medline established 79 papers of relevance. Data extraction and assessment followed the PRISMA workflow.
RESULTS
Based on specific criteria, 11 studies totalling 821 participants were included in this review. CD163 was quantified in various forms including soluble, cell surface, and mRNA measures. This review found that soluble CD163 was upregulated in diabetes complications in various local body fluids and systemically in plasma or serum and therefore implicated in the progression of those complications. CD163+ cells and mRNA were variably expressed across diabetes complications.
CONCLUSIONS
CD163 was altered in series of diabetes complications and the circulating sCD163 has potential utility as an inflammation biomarker. The variable expression of CD163 on cell surfaces and its mRNA across different diabetes complications warrants further systematic investigation.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Diabetes Complications; Diabetes Mellitus; Humans; Inflammation; Monocytes; RNA, Messenger; Receptors, Cell Surface
PubMed: 35190247
DOI: 10.1016/j.jdiacomp.2022.108150 -
BMC Pediatrics Jun 2023To compare the performance of Neutrophil-to-Lymphocyte Ratio (NLR) with that of Platelet-to-Lymphocyte Ratio (PLR) in diagnosing neonatal sepsis (NS). (Meta-Analysis)
Meta-Analysis
PURPOSE
To compare the performance of Neutrophil-to-Lymphocyte Ratio (NLR) with that of Platelet-to-Lymphocyte Ratio (PLR) in diagnosing neonatal sepsis (NS).
METHODS
PubMed and Embase were searched for relevant studies from the inception of the databases to May, 2022. The pooled sensitivity (SEN), specificity (SPE), and area under the receiver operator characteristic curve (AUC) were measured.
RESULTS
Thirteen studies involving 2610 participants were included. The SEN, SPE, and AUC of NLR were 0.76 (95%CI: 0.61-0.87), 0.82 (95%CI: 0.68-0.91), and 0.86 (95%CI: 0.83-0.89), respectively, and those of PLR were 0.82 (95%CI: 0.63-0.92), 0.80 (95%CI: 0.24-0.98), and 0.87 (95%CI: 0.83-0.89), respectively. Significant heterogeneity was observed among the studies. Subgroup analysis and meta-regression showed that types of sepsis (p = 0.01 for SEN), gold standard (p = 0.03 for SPE), and pre-set threshold (p<0.05 for SPE) might be the sources of heterogeneity for NLR, whereas the pre-set threshold (p<0.05 for SPE) might be the source of heterogeneity for PLR.
CONCLUSIONS
NLR and PLR would be of great accuracy for the diagnosis of NS, and the two indicators have similar diagnostic performance. However, the overall risk of bias was high, and significant heterogeneity was identified among the included studies. The results of this study should be interpreted prudently, and the normal or cut-off values and the type of sepsis should be considered. More prospective studies are needed to further support the clinical application of these findings.
Topics: Infant, Newborn; Humans; Neonatal Sepsis; Neutrophils; Sepsis; Blood Platelets; Lymphocytes
PubMed: 37391699
DOI: 10.1186/s12887-023-04094-y