RESUMEN
Chronic wasting disease (CWD) is a transmissible and fatal prion disease that affects cervids. While both oral and nasal routes of exposure to prions cause disease, the spatial and temporal details of how prions enter the central nervous system (CNS) are unknown. Carotid bodies (CBs) are structures that are exposed to blood-borne prions and are densely innervated by nerves that are directly connected to brainstem nuclei, known to be early sites of prion neuroinvasion. All CBs examined contained mast cells expressing the prion protein which is consistent with these cells playing a role in neuroinvasion following prionemia.
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Cuerpo Carotídeo , Ciervos , Ganglios Linfáticos , Mastocitos , Priones , Animales , Mastocitos/metabolismo , Mastocitos/patología , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Priones/metabolismo , Cuerpo Carotídeo/metabolismo , Cuerpo Carotídeo/patología , Ganglios/metabolismo , Ganglios/patología , Enfermedad Debilitante Crónica/metabolismo , Enfermedad Debilitante Crónica/patologíaRESUMEN
Marfan syndrome (MFS) is a hereditary condition accompanied by disorders in the structural and regulatory properties of connective tissue, including elastic fibers, due to a mutation in the gene encodes for fibrillin-1 protein (FBN1 gene) and the synthesis of abnormal fibrillin-1 glycoprotein. Despite the high potential of mast cells (MCs) to remodel the extracellular matrix (ECM), their pathogenetic significance in MFS has not been considered yet. The group of patients with Marfan syndrome included two mothers and five children (three girls aged 4, 11, and 11 and two boys aged 12 and 13). Normal skin was examined in two children aged 11 and 12. Histochemical, monoplex, and multiplex immunohistochemical techniques; combined protocols of simultaneous histochemical and immunohistochemical staining (the results of staining were assessed using light, epifluorescence, and confocal microscopy); and bioinformatics algorithms for the quantitative analysis of detected targets were used to evaluate mast cells and their relationship with other cells from extracellular structures in the skin dermis. Analysis of the skin MC population in children with Marfan syndrome revealed a considerably increased number of intra-organic populations with the preservation of the specific Tryptase+Chymase+CPA3+ protease profile typical of the skin. The features of the MC histotopography phenotype in MFS consisted of closer colocalization with elastic fibers, smooth muscle cells, and fibroblasts. MCs formed many intradermal clusters that synchronized the activity of cell functions in the stromal landscape of the tissue microenvironment with the help of spatial architectonics, including the formation of cell chains and the creation of fibrous niches. In MCs, the expression of specific proteases, TGF-ß, and heparin increased, with targeted secretion of biologically active substances relative to the dermal elastic fibers, which had specific structural features in MFS, including abnormal variability in thickness along their entire length, alternating thickened and thinned areas, and uneven surface topography. This paper discusses the potential role of MCs in strain analysis (tensometry) of the tissue microenvironment in MFS. Thus, the quantitative and qualitative rearrangements of the skin MC population in MFS are aimed at altering the stromal landscape of the connective tissue. The results obtained should be taken into account when managing clinical signs of MFS manifested in other pathogenetically critical structures of internal organs, including the aorta, tendons, cartilage, and parenchymal organs.
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Dermis , Tejido Elástico , Síndrome de Marfan , Mastocitos , Humanos , Síndrome de Marfan/metabolismo , Síndrome de Marfan/patología , Síndrome de Marfan/genética , Mastocitos/metabolismo , Mastocitos/patología , Niño , Masculino , Femenino , Tejido Elástico/metabolismo , Tejido Elástico/patología , Preescolar , Dermis/patología , Dermis/metabolismo , Adolescente , Fibrilina-1/metabolismo , Fibrilina-1/genética , Piel/metabolismo , Piel/patología , Matriz Extracelular/metabolismo , AdipoquinasRESUMEN
BACKGROUND: Altered biosynthesis of eicosanoids is linked to type 2 inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP), but their role in recalcitrant NPs is unclear. OBJECTIVES: We sought to identify endotypes that are linked to recalcitrant CRSwNP, based on eicosanoids, their biosynthetic enzymes, and receptors as well as cytokines and the presence of eosinophils and mast cells in recurrent NPs. METHODS: Mucosal tissue collected at the time of sinus surgery from 54 patients with CRSwNP and 12 non-CRS controls were analysed for leukotriene (LT) E4, prostaglandin (PG) D2, 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) and 17 cytokines with ELISAs and Bio-Plex immunoassays. Patient subgroups were identified by cluster analysis and the probability of NP recurrence were tested with logistic regression analyses. Gene expressions were analysed with qPCR. Tryptase and eosinophil-derived neurotoxin (EDN) were measured with ELISAs as indications of the presence of mast cells and eosinophils, respectively. RESULTS: Clustering of patients showed that an inflammatory signature characterised by elevated LTE4, PGD2, 15(S)-HETE and IL-13 was associated with NP recurrence. Previous NP surgery as well as aspirin-exacerbated respiratory disease were significantly more common among these patients. Expression of cyclooxygenase 1 was the only gene associated with NP recurrence. Levels of EDN, but not tryptase, were significantly higher in patients with recurrent NPs. CONCLUSION: Distinguishing endotypes that include LTE4, PGD2, 15HETE and conventional biomarkers of type 2 inflammation could help predict recurrent nasal polyposis and thus identify cases of recalcitrant CRSwNP.
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Biomarcadores , Ácidos Hidroxieicosatetraenoicos , Leucotrieno E4 , Pólipos Nasales , Prostaglandina D2 , Recurrencia , Rinitis , Sinusitis , Humanos , Sinusitis/metabolismo , Sinusitis/patología , Sinusitis/cirugía , Sinusitis/diagnóstico , Pólipos Nasales/metabolismo , Pólipos Nasales/patología , Pólipos Nasales/cirugía , Pólipos Nasales/genética , Femenino , Masculino , Leucotrieno E4/metabolismo , Persona de Mediana Edad , Enfermedad Crónica , Ácidos Hidroxieicosatetraenoicos/metabolismo , Adulto , Rinitis/metabolismo , Rinitis/patología , Rinitis/diagnóstico , Rinitis/cirugía , Biomarcadores/metabolismo , Prostaglandina D2/metabolismo , Pronóstico , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Eosinófilos/metabolismo , Eosinófilos/patología , Mastocitos/metabolismo , Mastocitos/patología , RinosinusitisRESUMEN
The role of mast cell (MC), a common myeloid-derived immune cell, in the development of oral squamous cell carcinoma (OSCC) is unclear. The aim of this study was to investigate MC infiltration in oral precancer and oral cancer. The evaluation of immune cell infiltration and its association with prognosis in OSCC used RNA sequencing and multiple public datasets. Multiplex immunofluorescence was used to explore the infiltration of MC in the microenvironment of OSCC and oral precancer and the interaction with CD8+ cells. The role of MC in OSCC progression was verified by in vivo experiments. The resting MC infiltration was mainly present in oral precancer, whereas activated MC infiltration was significantly higher in OSCC. Activated MC was associated with malignant transformation of oral precancer and poor prognosis of OSCC. In vivo studies showed that MC promoted the growth of OSCC. The infiltration of activated MC was negatively correlated with the infiltration of CD8+ T cells. The subtype of MC containing tryptase without chymase (MCT) was significantly higher in OSCC compared with oral precancer and was associated with poor survival. Furthermore, spatial distance analysis revealed a greater distance between MCT and CD8+ cells, which was also linked to poor prognosis in OSCC. Cox regression analysis showed that MCT could be a potential diagnostic and prognostic biomarker. This study provides new insights into the role of MC in the immune microenvironment of OSCC. It might enhance the immunotherapeutic efficacy of OSCC by developing targeted therapies against MC. SIGNIFICANCE: In this study, we investigated the role of mast cells (MC) in oral precancer and oral cancer and demonstrated that MCs are involved in oral cancer progression and may serve as a potential diagnostic and prognostic marker. It might improve the immunotherapeutic efficacy through developing targeted therapies against MCs.
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Transformación Celular Neoplásica , Progresión de la Enfermedad , Mastocitos , Neoplasias de la Boca , Lesiones Precancerosas , Microambiente Tumoral , Mastocitos/patología , Mastocitos/inmunología , Neoplasias de la Boca/patología , Neoplasias de la Boca/inmunología , Neoplasias de la Boca/mortalidad , Humanos , Microambiente Tumoral/inmunología , Transformación Celular Neoplásica/inmunología , Transformación Celular Neoplásica/patología , Lesiones Precancerosas/patología , Lesiones Precancerosas/inmunología , Pronóstico , Animales , Linfocitos T CD8-positivos/inmunología , Ratones , Masculino , Triptasas/metabolismo , Triptasas/genética , Femenino , Quimasas/metabolismo , Quimasas/genética , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patologíaRESUMEN
The prognostic significance of angiogenesis has been demonstrated in various types of cancer. However, in colorectal cancer (CRC), there are conflicting results regarding the relationship between angiogenesis and clinical-histopathological prognostic factors. Mast cells are immune system cells found in the inflammatory microenvironment; their role in carcinogenesis and prognosis remains unclear although they are considered to cause cancer development and progression. The present study aims to evaluate the prognostic significance of mast cell accumulation and angiogenesis assessed by microvessel density (MVD) in patients with CRC. Patients who underwent curative resection and who were not treated with neoadjuvant chemotherapy were included. The anti-CD34 antibody and anti-CD117 antibody were utilized for the immunohistochemical assessment of MVD and the mast cell count (MCC) in the tissue samples, respectively. The relationship between MCC, MVD, survival and clinical-histopathological prognostic factors were evaluated. A total of 94 patients were enrolled to the study. In a median 49-month follow-up, 65 patients (69.1%) died. The 5-year disease-free survival was 61.1% and 31.3% for the group with CD34â <â 18.3% and CD34â >â 18.3%, respectively (Pâ =â .001). The same groups presented 5-year overall survival rates of 77, 1% and 51, 4%, respectively (P, .012). The MVD was found to be associated with the pathological T stage, lymph node metastasis and distant metastasis (Pâ <â .05). Although the MCC was positively correlated with MVD, there was no association between the MCC and clinical-histopathological prognostic factors. MVD-assessed angiogenesis was significantly related to survival and the clinical-histopathological prognostic factors in patients diagnosed with CRC.
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Neoplasias Colorrectales , Mastocitos , Densidad Microvascular , Neovascularización Patológica , Proteínas Proto-Oncogénicas c-kit , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/mortalidad , Masculino , Femenino , Mastocitos/patología , Persona de Mediana Edad , Pronóstico , Anciano , Neovascularización Patológica/patología , Proteínas Proto-Oncogénicas c-kit/metabolismo , Adulto , Antígenos CD34/metabolismo , Inmunohistoquímica , Supervivencia sin Enfermedad , Anciano de 80 o más AñosRESUMEN
Merkel cell carcinoma (MCC) is a rare, highly aggressive, primitive neuroendocrine carcinoma of the skin, the origin of which is not yet fully understood. Numerous independent prognostic factors have been investigated in an attempt to understand which are the most important parameters to indicate in the histological diagnostic report of MCC. Of these, mast cells have only been studied in one paper before this one. We present a retrospective descriptive study of 13 cases of MCC, received at the Department of Pathology over a 20-year period (2003-2023 inclusive) on which we performed a study using whole-slide (WSI) morphometric analysis scanning platform Aperio Scanscope CS for the detection and spatial distribution of mast cells, using monoclonal anti-tryptase antibody and anti-CD34 monoclonal antibody to study the density of microvessels. In addition, we analyzed MCPyV status with the antibody for MCPyV large T-antigen (Clone CM2B4). We found statistically significant correlation between mast cell density and local recurrence/distant metastasis/death-of-disease (p = 0.008). To our knowledge, we firstly reported that MCPyV ( -) MCC shows higher mast cells density compared to MCPyV ( +) MCC, the latter well known to be less aggressive. Besides, the median vascular density did not show no significant correlation with recurrence/metastasis/death-of-disease, (p = 0.18). Despite the small sample size, this paper prompts future studies investigating the role of mast cell density in MCC.
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Carcinoma de Células de Merkel , Mastocitos , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/patología , Mastocitos/patología , Mastocitos/inmunología , Masculino , Estudios Retrospectivos , Femenino , Anciano , Proyectos Piloto , Pronóstico , Anciano de 80 o más Años , Persona de Mediana Edad , Neoplasias Cutáneas/patología , Poliomavirus de Células de Merkel , Recuento de CélulasRESUMEN
Inclusion body myositis is the commonest acquired myopathy in those over 50 years of age. Although it is classified as an idiopathic inflammatory myopathy and the most frequent finding on muscle biopsy in inclusion body myositis is an endomysial inflammatory infiltrate, it is clinically distinct from other myositis, including a lack of response to immunosuppressive medication. Neurogenic changes are commonly reported in inclusion body myositis and inflammatory changes are observed in muscle following neurogenic injury. The objective of our study was to explore whether neurogenic inflammation plays a role in the pathogenesis of inclusion body myositis, possibly explaining its resistance to immunosuppression. The number of mast cells and presence of neuropeptides, substance P and calcitonin gene-related peptide, were assessed in 48 cases of inclusion body myositis, 11 cases of steroid responsive myositis, two cases of focal myositis associated with neurogenic injury, and ten normal controls. The number of mast cells in inclusion body myositis focal and myositis associated to neurogenic injury were significantly greater than that observed in steroid responsive myositis. Our findings suggest that neurogenic inflammation mediated through mast cells may play a role in the pathogenesis of inclusion body myositis, and focal myositis associated to neurogenic injury, and thus, explain in some part its lack of response to immunosuppressive treatments.
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Mastocitos , Miositis por Cuerpos de Inclusión , Humanos , Miositis por Cuerpos de Inclusión/patología , Miositis por Cuerpos de Inclusión/tratamiento farmacológico , Mastocitos/patología , Mastocitos/efectos de los fármacos , Femenino , Persona de Mediana Edad , Masculino , Anciano , Anciano de 80 o más Años , Sustancia P/metabolismo , Músculo Esquelético/patología , Péptido Relacionado con Gen de Calcitonina/metabolismo , Adulto , Inmunosupresores/uso terapéutico , Inmunosupresores/farmacologíaRESUMEN
INTRODUCTION: The diagnosis of eosinophilic gastrointestinal diseases is largely based on mucosal eosinophil counts, but thresholds and normal ranges beyond the esophagus are debated, calling for much-needed methodological standardization. We aimed to develop a standardized workflow for duodenal cell quantification and estimate duodenal eosinophil and mast cell numbers in healthy controls. METHODS: Software-based histological cell quantification using free-sized or fixed-sized regions was developed and applied to digitized hematoxylin and eosin (H&E)-stained slides from 58 individuals (healthy controls [HCs] and patients with functional dyspepsia). Intraclass correlation coefficients (ICCs) compared inter-rater reliability between software-based and microscopic quantification. Reproducibility of the software-based method was validated in an independent cohort of 37 control and functional dyspepsia subjects. Eosinophil identification on H&E staining was compared to immunohistochemistry (IHC). Normal eosinophil (H&E) and mast cell (cKit) ranges were determined in 70 adult HCs. RESULTS: Eosinophil quantification on digitized slides demonstrated excellent (ICC = 0.909) and significantly improved reproducibility over microscopic evaluation (ICC = 0.796, P = 0.0014), validated in an independent cohort (ICC = 0.910). Duodenal eosinophils were more abundant around crypts than in villi ( P < 0.0001), while counts were similar on matched H&E- and IHC-stained slides ( P = 0.55). Mean ± SD (95th percentile) duodenal eosinophils and mast cells in HC were 228.8/mm 2 ± 94.7 (402.8/mm 2 ) and 419.5/mm 2 ± 132.2 (707.6/mm 2 ), respectively. DISCUSSION: We developed and validated a standardized approach to duodenal histological cell quantification, generalizable to various mucosal cell types. Implementation of software-based quantification identified 400 eosinophils/mm 2 and 700 mast cells/mm 2 as thresholds for abnormal duodenal infiltration.
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Duodeno , Eosinófilos , Mastocitos , Programas Informáticos , Humanos , Eosinófilos/patología , Eosinófilos/citología , Duodeno/patología , Duodeno/citología , Mastocitos/patología , Reproducibilidad de los Resultados , Adulto , Masculino , Femenino , Persona de Mediana Edad , Eosinofilia/patología , Eosinofilia/diagnóstico , Recuento de Células , Recuento de Leucocitos/métodos , Inmunohistoquímica , Dispepsia/patología , Dispepsia/diagnóstico , Mucosa Intestinal/patología , Mucosa Intestinal/citología , Anciano , Estudios de Casos y Controles , Adulto Joven , Variaciones Dependientes del ObservadorRESUMEN
BACKGROUND/AIM: Ovarian cancer (OVC) is a common, aggressive, and heterogeneous malignancy, with a widely variable prognosis. With the advances of modern immunology, mast cells (MCs) have been shown to play a significant role in the prognosis of some malignant tumors. However, the role of mast cells in the prognosis of OVC is unknown. MATERIALS AND METHODS: In this study, MC-associated prognostic genes (MRGs) were used to classify OVC from The Cancer Genome Atlas (TCGA)-OVC cohort. Genes were evaluated using univariate cox regression analysis. Twenty-nine prognostic gene signatures were identified using LASSO-COX analysis. COX regression models and principal component analysis (PCA) algorithms were used to construct MRG scores and individual MRGs patterns. External validation was performed in the TCGA-breast cancer (BRCA) and IMvigor210 cohorts. Immunity analysis based on MRGs was performed using CIBERSORT, and GSVA methods, and immunotherapy response was evaluated using the TIDE website. RESULTS: Using TCGA-OVC data, we established a model for constructing MRG scores based on the twenty-nine identified prognostic gene signatures using the PCA algorithm. MRG scores were found to be strongly correlated with immune cell infiltration and were excellent predictors of prognosis in patients with OVC. Low MRG scores were associated with better prognosis and better response to immunotherapy and chemotherapy. CONCLUSION: MC-related prognosis signature characterizes the immune landscape and predicts the prognosis of OVC. Understanding the correlation between MC-related gene signatures and immunotherapy and chemotherapy may improve the development of personalized clinical treatment strategies.
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Mastocitos , Neoplasias Ováricas , Humanos , Femenino , Mastocitos/inmunología , Mastocitos/patología , Pronóstico , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Biomarcadores de Tumor/genética , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica , Inmunoterapia/métodos , Perfilación de la Expresión Génica , TranscriptomaRESUMEN
Infertility is an important personal and society disease, of which the male factor represents half of all causes. One of the aspects less studied in male infertility is the immunological testicular microenvironment. Mast cells (MCs), having high potential for regulating spermatogenesis due to fine-tuning the state of the integrative buffer metabolic environment, are one of the most crucial cellular subpopulations of the testicular interstitium. One important component of the MC secretome is proteases that can act as proinflammatory agents and in extracellular matrix (ECM) remodeling. In the testis, MCs are an important cell component of the testicular interstitial tissue (TIT). However, there are still no studies addressing the analysis of a specific MC protease-carboxypeptidase A3 (CPA3)-in cases with altered spermatogenesis. The cytological and histotopographic features of testicular CPA3+ MCs were examined in a study involving 34 men with azoospermia. As revealed, in cases with non-obstructive azoospermia, a higher content of CPA3+ MCs in the TIT and migration to the microvasculature and peritubular tissue of seminiferous tubules were observed when compared with cases with obstructive azoospermia. Additionally, a high frequency of CPA3+ MCs colocalization with fibroblasts, Leydig cells, and elastic fibers was detected in cases with NOA. Thus, CPA3 seems to be of crucial pathogenetic significance in the formation of a profibrogenic background of the tissue microenvironment, which may have direct and indirect effects on spermatogenesis.
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Azoospermia , Mastocitos , Testículo , Adulto , Humanos , Masculino , Azoospermia/patología , Azoospermia/metabolismo , Carboxipeptidasas A/metabolismo , Mastocitos/metabolismo , Mastocitos/patología , Espermatogénesis , Testículo/metabolismo , Testículo/patologíaRESUMEN
BACKGROUND: Bronchoalveolar lavage (BAL) cytology results from 1 lung might not be representative of both lungs. OBJECTIVES: To determine whether the lung site sampled would influence the horse's BAL cytology profile, and if a pooled BAL sample would be superior with regard to BAL cytology diagnosis in a cohort of healthy and subclinical asthmatic warmblood horses. ANIMALS: Fifty-nine horses in 2021 and 70 horses in 2022, the follow-up included 53 of the same in each year. METHODS: A cross-sectional study with follow-up included BAL cytology samples from individual lungs and from pooled BAL samples. The BAL samples were enumerated and differential cell count were applied to categorize the horses as control or with airway inflammation (AI). RESULTS: Bronchoalveolar lavage mast cell count was higher in left lung compared to right lung (2021; median 1.6 [range, 0.6-3.3] vs 1.2 [0.7-1.5] P = .009, 2022; median 3.1 [2.1-4.2] vs 2.4 [1.7-3.4], P < .001) and compared to pooled samples (2022; median 2.6 [1.7-3.7], P < .001). Between year 2021 and 2022, 17 of the horses had changes in BAL cytology from control to AI or vice versa. CONCLUSIONS AND CLINICAL IMPORTANCE: Pooled BAL sample was the least reliable for detecting AI, and was not representative of the overall lung condition.
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Líquido del Lavado Bronquioalveolar , Lavado Broncoalveolar , Enfermedades de los Caballos , Animales , Caballos , Líquido del Lavado Bronquioalveolar/citología , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/diagnóstico , Estudios Transversales , Masculino , Femenino , Lavado Broncoalveolar/veterinaria , Pulmón/citología , Pulmón/patología , Asma/veterinaria , Asma/patología , Mastocitos/citología , Mastocitos/patología , Recuento de Células/veterinaria , CitologíaRESUMEN
ABSTRACT: Molecular measurable residual disease can persist in core-binding factor acute myeloid leukemia in otherwise disease-free patients. Utilizing cell sorting followed by fluorescent in situ hybridization, we show that detection is due to mast cells.
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Citometría de Flujo , Leucemia Mieloide Aguda , Mastocitos , Neoplasia Residual , Proteínas de Fusión Oncogénica , Humanos , Mastocitos/metabolismo , Mastocitos/patología , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Citometría de Flujo/métodos , Neoplasia Residual/diagnóstico , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Hibridación Fluorescente in Situ , Proteína 1 Compañera de Translocación de RUNX1/genética , Proteína 1 Compañera de Translocación de RUNX1/metabolismo , Masculino , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , FemeninoRESUMEN
The insights provided by in-situ detection of immune cells within hepatocellular carcinoma (HCC) might present information on patient outcomes. Studies investigating the expression and localization of immune cells within tumor tissues are associated with several challenges, including a lack of precise annotation for tumor regions and random selection of microscopic fields of view. QuPath is an open-source, user-friendly software that could meet the growing need for digital pathology in whole-slide image (WSI) analysis. The infiltration of HCC and adjacent tissues by CD1a+ immature dendritic cells (iDCs), CD117+ mast cells, and NKp46+ natural killer cells (NKs) cells was assessed immunohistochemically in representative specimens of 67 patients with HCC who underwent curative resection. The area fraction (AF) of positively stained cells was assessed automatically in WSIs using QuPath in the tumor center (TC), inner margin (IM), outer margin (OM), and peritumor (PT) area. The prognostic significance of immune cells was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). The AF of mast cells was significantly greater than the AF of NKs, and the AF of iDCs was significantly lower compared to NKs in each region of interest. High AFs of mast cells in the IM and PT areas were associated with longer DFS. In addition, high AF of mast cells in IM was associated with longer OS. Computer-assisted analysis using this software is a suitable tool for obtaining prognostic information for tumor-infiltrating immune cells (iDCs, mast cells, and NKs) in different regions of HCC after resection. Mast cells displayed the greatest AF in all regions of interest (ROIs). Mast cells in the peritumor region and IM showed a positive prognostic significance.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Mastocitos , Programas Informáticos , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/cirugía , Mastocitos/patología , Mastocitos/inmunología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Pronóstico , Microambiente Tumoral/inmunología , Masculino , Persona de Mediana Edad , Procesamiento de Imagen Asistido por Computador/métodos , Femenino , AncianoRESUMEN
BACKGROUND/AIM: Warthin's tumor, the second most frequent neoplasia of the parotid gland, is characterized by a proliferation of both epithelial and lymphoid components. In addition to epithelial and lymphoid cells, various other cell types are implicated to varying degrees in the immune response. Notably, mast cells have long been recognized as a consistent cell population within this tumor. Despite the historical acknowledgment of mast cell presence, their true distribution and significance within Warthin's tumor remain unclear. In this study, we aimed to elucidate the distribution and significance of mast cells in Warthin's tumor. MATERIALS AND METHODS: Histochemical and immunohistochemical methods were employed for the evaluation of mast cells within tumor specimens. RESULTS: Our study revealed a notable concentration of mast cells in the epithelial component of Warthin's tumor. Microscopic examination showed predominant lymphoid and epithelial elements with occasional cystic formations. Immunohistochemical analysis identified mast cells in both components, emphasizing their role in the tumor microenvironment. Double immunostaining (mast cell tryptase and CD34) revealed no significant correlation between mast cells and blood vessels. Intraepithelial mast cells (IEMCs) had a significantly higher density in the epithelial component, suggesting a potential association with the tumor's benign nature. The relationship between IEMCs and epithelial cells, especially in the presence of cystic structures, offers valuable insights into the unique features of Warthin's tumor. CONCLUSION: Our study contributes to the understanding of mast cells in Warthin's tumor, highlighting a substantial concentration within the epithelial component. This knowledge may pave the way for further investigations into the roles of mast cells in the pathogenesis and treatment of Warthin's tumor.
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Adenolinfoma , Inmunohistoquímica , Mastocitos , Mastocitos/patología , Mastocitos/inmunología , Adenolinfoma/patología , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Microambiente Tumoral/inmunología , Recuento de Células , Neoplasias de la Parótida/patología , Adulto , Células Epiteliales/patología , Células Epiteliales/metabolismoRESUMEN
Recent studies suggested the potential role of mast cells (MCs) in the pathology of coronavirus disease 2019 (COVID-19). However, the precise description of the MCs' activation and the engagement of their proteases is still missing. The objective of this study was to further reveal the importance of MCs and their proteases (chymase, tryptase, and carboxypeptidase A3 (CPA3)) in the development of lung damage in patients with COVID-19. This study included 55 patients who died from COVID-19 and 30 controls who died from external causes. A histological analysis of the lung parenchyma was carried out to assess the protease profiles and degranulation activity of MCs. In addition, we have analyzed the general blood test, coagulogram, and C-reactive protein. The content of tryptase-positive MCs (Try-MCs) in the lungs of patients with COVID-19 was higher than in controls, but their degranulation activity was lower. The indicators of chymase-positive MCs (Chy-MCs) were significantly lower than in the controls, while the content of CPA3-positive MCs (CPA3-MCs) and their degranulation activity were higher in patients with COVID-19. In addition, we have demonstrated the existence of correlations (positive/negative) between the content of Try-MCs, Chy-MCs, and CPA3-MCs at different states of their degranulation and presence (co-adjacent/single) and the levels of various immune cells (neutrophils, eosinophils, basophils, and monocytes) and other important markers (blood hemoglobin, activated partial thromboplastin time (aPTT), international normalized ratio (INR), and fibrinogen). Thus, the identified patterns suggest the numerous and diverse mechanisms of the participation of MCs and their proteases in the pathogenesis of COVID-19, and their impact on the inflammatory process and coagulation status. At the same time, the issue requires further study in larger cohorts of patients, which will open up the possibility of using drugs acting on this link of pathogenesis to treat lung damage in patients with COVID-19.
Asunto(s)
COVID-19 , Pulmón , Mastocitos , SARS-CoV-2 , Triptasas , Humanos , COVID-19/inmunología , COVID-19/patología , Mastocitos/patología , Mastocitos/inmunología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Triptasas/metabolismo , Pulmón/patología , Pulmón/virología , Pulmón/inmunología , Degranulación de la Célula , Quimasas/metabolismo , Carboxipeptidasas A/metabolismo , Adulto , Anciano de 80 o más Años , Estudios de Casos y ControlesRESUMEN
Mast cells are tissue-resident immune cells strategically located in different compartments of the normal human heart (the myocardium, pericardium, aortic valve, and close to nerves) as well as in atherosclerotic plaques. Cardiac mast cells produce a broad spectrum of vasoactive and proinflammatory mediators, which have potential roles in inflammation, angiogenesis, lymphangiogenesis, tissue remodelling, and fibrosis. Mast cells release preformed mediators (e.g. histamine, tryptase, and chymase) and de novo synthesized mediators (e.g. cysteinyl leukotriene C4 and prostaglandin D2), as well as cytokines and chemokines, which can activate different resident immune cells (e.g. macrophages) and structural cells (e.g. fibroblasts and endothelial cells) in the human heart and aorta. The transcriptional profiles of various mast cell populations highlight their potential heterogeneity and distinct gene and proteome expression. Mast cell plasticity and heterogeneity enable these cells the potential for performing different, even opposite, functions in response to changing tissue contexts. Human cardiac mast cells display significant differences compared with mast cells isolated from other organs. These characteristics make cardiac mast cells intriguing, given their dichotomous potential roles of inducing or protecting against cardiovascular diseases. Identification of cardiac mast cell subpopulations represents a prerequisite for understanding their potential multifaceted roles in health and disease. Several new drugs specifically targeting human mast cell activation are under development or in clinical trials. Mast cells and/or their subpopulations can potentially represent novel therapeutic targets for cardiovascular disorders.