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Oral Oncology Jun 2019Tumor associated macrophages (TAMs) are among the most abundant cells of the tumor microenvironment. Several studies have been performed to investigate whether TAM... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Tumor associated macrophages (TAMs) are among the most abundant cells of the tumor microenvironment. Several studies have been performed to investigate whether TAM markers, namely CD68 and CD163, could serve as prognostic factors in patients with squamous cell carcinoma of the head and neck (SCCHN). The aim of this systematic review and meta-analysis was to synthetize the available evidence of the literature about the role of CD68+ and CD163+ TAMs as prognostic factors in SCCHN.
MATERIALS AND METHODS
This systematic review was performed according to the guidelines reported in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Meta-analysis of overall survival, disease-free survival and progression-free survival was performed using the inverse of variance test. A random- or a fixed- effect model was used on the basis of the presence of heterogeneity. Risk of bias assessment and subgroup analysis were also performed.
RESULTS
High stromal expression of CD163+ TAMs correlated with both poor overall survival (HR, 2.26; 95% CI: [1.47, 3.47]; P < 0.001) and progression-free survival (HR, 2.29; 95% CI: [1.11, 4.71]; P = 0.03). Conversely, abundance of CD68+ TAMs was not associated with overall survival (HR, 1.25; 95% CI: [0.86, 1.80]; P = 0.24) and disease-free survival (HR, 2.06; 95% CI: [0.84, 5.05]; P = 0.11).
CONCLUSIONS
Findings from this study revealed that whilst IHC analysis of the generic macrophage marker CD68+ has no prognostic utility in patients with SCCHN, the M2-like marker CD163+ predicts poor prognosis. Our data suggest that assessment of CD163+ TAMs in SCCHN has potential for future clinical use. Further well-standardized studies should be performed to confirm these results.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Cancer-Associated Fibroblasts; Disease Progression; Female; Head and Neck Neoplasms; Humans; Male; Prognosis; Receptors, Cell Surface; Squamous Cell Carcinoma of Head and Neck; Survival Analysis; Tumor Microenvironment
PubMed: 31109698
DOI: 10.1016/j.oraloncology.2019.04.019 -
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 -
Critical Reviews in Oncology/hematology Jul 2015Erdheim-Chester disease (ECD) is a rare form of non-Langerhans-cell histiocytosis, associated in more than 50% of cases to BRAF(V600E) mutations in early multipotent... (Review)
Review
Erdheim-Chester disease (ECD) is a rare form of non-Langerhans-cell histiocytosis, associated in more than 50% of cases to BRAF(V600E) mutations in early multipotent myelomonocytic precursors or in tissue-resident histiocytes. It encompasses a spectrum of disorders ranging from asymptomatic bone lesions to multisystemic, life-threatening variants. We reviewed all published reports of histologically-confirmed ECD and explored clinical, radiological, prognostic and therapeutic characteristics in a population of 448 patients, including a unique patient from our Department. To find a clinically relevant signature defining differentiated prognostic profiles, the patients' disease features were compared in relation to their CNS involvement that occurred in 56% of the entire population. Diabetes insipidus, visual disturbances, pyramidal and extra-pyramidal syndromes were the most recurrent neurological signs, whereas concomitant pituitary involvement, retro-orbital masses and axial lesions in the presence of symmetric bilateral osteosclerosis of long bones depicted the typical ECD clinical picture. Patients with CNS infiltration showed a lower occurrence of heart involvement and a higher incidence of bone, skin, retro-peritoneal, lung, aortic and renal infiltration. No difference in the therapeutic algorithm was found after stratification for CNS involvement. A better understanding of the disease pathogenesis, including BRAF deregulation, in keeping with improved prognostic criteria, will provide novel suggestions for the management of ECD.
Topics: Adrenal Cortex Hormones; Adult; Bone and Bones; Central Nervous System; Erdheim-Chester Disease; Humans; Kidney; Male; Myocardium; Point Mutation; Prognosis; Proto-Oncogene Proteins B-raf
PubMed: 25744785
DOI: 10.1016/j.critrevonc.2015.02.004 -
Journal of Oral Pathology & Medicine :... May 2018Oral Squamous Cell Carcinoma (OSCC) presents a tumor microenvironment rich in inflammatory cells. Depending on the stimulus, macrophages can polarize in M1 or M2... (Meta-Analysis)
Meta-Analysis Review
Oral Squamous Cell Carcinoma (OSCC) presents a tumor microenvironment rich in inflammatory cells. Depending on the stimulus, macrophages can polarize in M1 or M2 profile, where M1 acts as proinflammatory and antitumor, and M2 is anti-inflammatory and shows protumor activity. Several studies have shown that macrophages are important to the prognosis of patients with different types of cancer. Our aim was to conduct a systematic review to evaluate the role of macrophages in the prognosis of OSCC patients. A search in the Pubmed, Scopus, and ISI Web of Knowledge database was performed, and it was included only studies that evaluated the importance of macrophages in the prognosis of OSCC patients. From initial 286 articles, 14 fully attended the inclusion criteria. In the majority of the articles, it was evaluated only CD68, a panmacrophage marker, or CD163, a M2 marker. Only one article evaluated the M1 marker, CD11c. Besides, 5 articles analyzed the presence of macrophages in different areas of the tumor. Higher concentrations of CD68 and CD163 were associated with worse survival. In conclusion, macrophages are important to OSCC patients' prognosis; however, it is necessary to address in which tumor region the presence of polarized macrophage is more important to the outcome.
Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma, Squamous Cell; Databases, Bibliographic; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Macrophages; Male; Middle Aged; Prognosis; Receptors, Cell Surface; Tumor Microenvironment; Young Adult
PubMed: 28940738
DOI: 10.1111/jop.12643 -
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 -
International Journal of Colorectal... Jul 2020Tumor-associated macrophages (TAMs) are key components of colorectal cancer (CRC) microenvironment, but their role in CRC prognosis is not fully defined. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tumor-associated macrophages (TAMs) are key components of colorectal cancer (CRC) microenvironment, but their role in CRC prognosis is not fully defined.
OBJECTIVE
This study aimed to evaluate prognostic value of different types and distribution of TAMs in CRC.
METHODS
Total 27 studies with 6115 patients were searched from PubMed and Embase and analyzed to determine the association between TAMs, including distinct TAM subsets and infiltration location, and CRC survival. The prognostic impact of TAMs on CRC was further stratified by tumor type and mismatch repair system (MMR) status.
RESULTS
A pooled analysis indicated that high density of TAMs in CRC tissue was significantly associated with favorable 5-year overall survival (OS) but not with disease-free survival (DFS). CD 68 TAM subset correlated with better 5-year OS, while neither CD68NOS2 M1 subset nor CD163 M2 subset was correlated with 5-year OS. Increased CD68 TAM infiltration in tumor stroma but not in tumor islet predicted improved 5-year OS. Stratification by tumor type and MMR status showed that in colon cancer or MMR-proficient CRC, elevated TAM density was associated with better 5-year OS.
CONCLUSIONS
High infiltration of CD68 TAMs could be a favorable prognostic marker in CRC. Future therapies stimulating CD68 TAM infiltration may be promising in CRC treatment.
Topics: Antigens, Differentiation, Myelomonocytic; Colonic Neoplasms; Humans; Macrophages; Prognosis; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 32303831
DOI: 10.1007/s00384-020-03593-z -
Leukemia & Lymphoma Sep 2023Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) chacaterized by persistent peripheral blood monocytosis,...
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) chacaterized by persistent peripheral blood monocytosis, hypercellular bone marrow and dysplasia at least in one myeloid lineage. CMML shares much of its molecular landscape with other myeloid neoplasms, while differs from others such as chronic neutrophilic leukemia (CNL), given the high frequency of CSF3R mutations in the latter. In this article, we report a case of CSF3R-mutated CMML and dissect this rare entity by reviewing the medical literature, with the intent to understand how this rare mutation shapes CMML's clinical and morphological phenotype. CSF3R-mutated CMML emerges as a rare entity meeting the ICC/WHO diagnostic criteria for CMML and simultaneously showing clinical-pathological and molecular traits of CNL and atypical chronic myeloid leukemia, rising an important and difficult diagnostic and therapeutical issue.
Topics: Humans; Leukemia, Myelomonocytic, Chronic; Leukemia, Neutrophilic, Chronic; Mutation; Myeloproliferative Disorders; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Prognosis; Receptors, Colony-Stimulating Factor
PubMed: 37395413
DOI: 10.1080/10428194.2023.2227750 -
Obesity Reviews : An Official Journal... Sep 2021This systematic review investigates the association of sCD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus (T2DM), insulin resistance, and... (Review)
Review
The association of soluble CD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus and its underlying physiological disorders: A systematic review.
This systematic review investigates the association of sCD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus (T2DM), insulin resistance, and beta-cell dysfunction. Sixteen studies (seven cross-sectional, two case-control, one nested case-control, three prospective cohort, and three experimental) were identified. Most studies demonstrated that elevated sCD163 concentrations were associated with increased insulin resistance. Cross-sectional, case-control, and nested case-control studies showed higher sCD163 in subjects with T2DM compared with healthy individuals. An 18-year follow-up prospective cohort study showed that elevated baseline sCD163 was a strong predictor of T2DM incidence. Prospective cohort studies demonstrated that baseline measures and longitudinal changes in sCD163 were positively associated with insulin resistance; however, associations with beta-cell function were inconsistent. Two experimental studies evaluated the relationship of sCD163 with T2DM and HOMA-IR after weight-reducing interventions. After very low-calorie diet treatments, sCD163 concentration declined significantly in patients with T2DM but was not associated with insulin resistance. Bariatric surgery did not significantly impact sCD163 levels. In a double-blind randomized controlled trial, resveratrol supplementation significantly reduced circulating sCD163 in T2DM patients. Current studies demonstrate the potential utility of sCD163 as an early biomarker of T2DM risk and highlight a potential mechanism linking obesity with T2DM onset.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Macrophage Activation; Prospective Studies; Randomized Controlled Trials as Topic; Receptors, Cell Surface
PubMed: 33913230
DOI: 10.1111/obr.13257 -
International Journal of Dermatology Oct 2023Myeloid neoplasms may metastasize to the skin, presenting a wide range of clinical-pathological features that often lead to a reduction in patients' survival. The... (Review)
Review
Cutaneous involvement in Ph-negative myeloproliferative neoplasms: from extramedullary hematopoiesis to myeloid metastasis with histiocytic differentiation. A systematic review of the literature.
Myeloid neoplasms may metastasize to the skin, presenting a wide range of clinical-pathological features that often lead to a reduction in patients' survival. The presentation varies depending on the category of myeloid neoplasm and its prognostic significance. The literature has specifically focused on the features of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelomonocytic leukemia (CMML). In this article, we aimed to uncover the peculiarities of clonal skin proliferations in the course of Ph-negative myeloproliferative neoplasms (MPNs). We conducted a systematic review and statistical analysis of the literature data. MPN patients mainly exhibited cutaneous extramedullary hematopoiesis, while a minority displayed cutaneous histiocytic lesions. Furthermore, these patients showed lower survival rates compared to the median survival of MPN patients, especially when calculating survival from the appearance of cutaneous lesions. Our work highlights, for the first time, the prognostic relevance and histological heterogeneity of cutaneous lesions in MPN. Moreover, it emphasizes the importance of dermatological and histological examinations when cutaneous lesions are present.
Topics: Humans; Hematopoiesis, Extramedullary; Hematologic Diseases; Leukemia, Myelomonocytic, Chronic; Physical Examination; Skin
PubMed: 37649236
DOI: 10.1111/ijd.16809 -
Annals of Hematology Mar 2018t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality involving the ETS transcription factor ETV6 and meningioma 1 (MN1) genes. In this study, we analyzed... (Review)
Review
t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality involving the ETS transcription factor ETV6 and meningioma 1 (MN1) genes. In this study, we analyzed the clinical, cytogenetic, and molecular features of five new patients with the t(12;22)/MN1-EVT6 who presented with acute myeloid leukemia or chronic myelomonocytic leukemia. We subsequently reviewed the literature and identified seven additional cases reported with t(12;22)/MN1-EVT6. Our data suggest that neoplasms carrying the t(12;22)/MN1-ETV6, although rare, can commonly present as myeloid neoplasms at the initial diagnosis, including acute myeloid leukemia (n = 8), myelodysplastic syndrome (n = 2), and myelodysplastic/myeloproliferative neoplasms (n = 2). There were five men and seven women with a median age of 43 years (range, 15-63 years) at initial diagnosis. Cytogenetics revealed t(12;22) as the sole abnormality in five patients, with the remaining seven patients harboring additional chromosomal aberrations. Of the five patients who received known therapy regimens, all of them had poor response to the idarubicin/mitoxantrone + cytarabine regimen. Of the seven patients with follow-up information, six patients died with a median overall survival time of only 5 months (range, 1-12 months) after the emergence of t(12;22). In summary, patients with t(12;22) are frequently associated with myeloid neoplasms, poor response to chemotherapy, and inferior outcome.
Topics: Adolescent; Adult; Bone Marrow Neoplasms; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 13; Female; Humans; Male; Middle Aged; Oncogene Proteins, Fusion; Proto-Oncogene Proteins c-ets; Repressor Proteins; Retrospective Studies; Trans-Activators; Translocation, Genetic; Tumor Suppressor Proteins; Young Adult; ETS Translocation Variant 6 Protein
PubMed: 29273914
DOI: 10.1007/s00277-017-3208-2