Diverse Macrophage Populations Contribute to the Inflammatory Microenvironment in Premalignant Lesions During Localized Invasion.
Ontology highlight
ABSTRACT:
SUBMITTER: Ibrahim AM
PROVIDER: S-EPMC7541939 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Diverse Macrophage Populations Contribute to the Inflammatory Microenvironment in Premalignant Lesions During Localized Invasion.
Ibrahim Ayman M AM Moss Matthew A MA Gray Zane Z Rojo Michelle D MD Burke Caitlin M CM Schwertfeger Kathryn L KL Dos Santos Camila O CO Machado Heather L HL
Frontiers in oncology 20200924
Myeloid cell heterogeneity remains poorly studied in breast cancer, and particularly in premalignancy. Here, we used single cell RNA sequencing to characterize macrophage diversity in mouse pre-invasive lesions as compared to lesions undergoing localized invasion. Several subpopulations of macrophages with transcriptionally distinct profiles were identified, two of which resembled macrophages in the steady state. While all subpopulations expressed tumor-promoting genes, many of the populations e ...[more]
Similar Datasets
Project description:BackgroundGraft-versus-host disease (GvHD) is a major life-threatening complication of allogeneic haematopoietic stem cell transplantation (HSCT), limiting the broad application of HSCT for haematological malignancies. Cutaneous GvHD is described as a post-transplant inflammatory reaction by skin-infiltrating donor T cells and remaining recipient tissue-resident memory T cells. Despite the major influence of lymphocytes on GvHD pathogenesis, the complex role of mononuclear phagocytes (MNPs) in tissues affected by GvHD is increasingly appreciated.ObjectivesTo characterize the identity, origin and functions of MNPs in patients with acute cutaneous GvHD.MethodsUsing single-cell RNA sequencing and multiplex tissue immunofluorescence, we identified an increased abundance of MNPs in skin and blood from 36 patients with acute cutaneous GvHD. In cases of sex-mismatched transplantation, we used expression of X-linked genes to detect rapid tissue adaptation of newly recruited donor MNPs resulting in similar transcriptional states of host- and donor-derived macrophages within GvHD skin lesions.ResultsWe showed that cutaneous GvHD lesions harbour expanded CD163+ tissue-resident macrophage populations with anti-inflammatory and tissue-remodelling properties including interleukin-10 cytokine production. Cell-cell interaction analyses revealed putative signalling to strengthen regulatory T-cell responses. Notably, macrophage polarization in chronic cutaneous GvHD types was proinflammatory and drastically differed from acute GvHD, supporting the notion of distinct cellular players in different clinical GvHD subtypes.ConclusionsOverall, our data reveal a surprisingly dynamic role of MNPs after HSCT. Specific and time-resolved targeting to repolarize this cell subset may present a promising therapeutic strategy in combatting GvHD skin inflammation.
| S-EPMC10873647 | biostudies-literature
Project description:Breast cancer (BC) prevention remains the ultimate cost-effective method to reduce the global burden of invasive breast cancer (IBC). To date, surgery and chemoprevention remain the main risk-reducing modalities for those with hereditary cancer syndromes, as well as high-risk non-hereditary breast lesions such as ADH, ALH, or LCIS. Ductal carcinoma in situ (DCIS) is a preinvasive malignant lesion of the breast that closely mirrors IBC and, if left untreated, develops into IBC in up to 50% of lesions. Certain high-risk patients with DCIS may have a 25% risk of developing recurrent DCIS or IBC, even after surgical resection. The development of breast cancer elicits a strong immune response, which brings to prominence the numerous advantages associated with immune-based cancer prevention over drug-based chemoprevention, supported by the success of dendritic cell vaccines targeting HER2-expressing BC. Vaccination against BC to prevent or interrupt the process of BC development remains elusive but is a viable option. Vaccination to intercept preinvasive or premalignant breast conditions may be possible by interrupting the expression pattern of various oncodrivers. Growth factors may also function as potential immune targets to prevent breast cancer progression. Furthermore, neoantigens also serve as effective targets for interception by virtue of strong immunogenicity. It is noteworthy that the immune response also needs to be strong enough to result in target lesion elimination to avoid immunoediting as it may occur in IBC arising from DCIS. Overall, if the issue of vaccine targets can be solved by interrupting premalignant lesions, there is a potential to prevent the development of IBC.
| S-EPMC8652247 | biostudies-literature
Project description:BackgroundCarcinogenesis is a dynamic process which traditional biopsying can not keep up with. Saliva as fluid in the vicinity of the tumor can offer better insights to this process. This study aimed to identify the accuracy of salivary DNA integrity index in differentiating between oral premalignant lesions and oral cancer.Material and methodsThis phase II diagnostic test accuracy study included 93 patients divided into three groups: 30 oral cancer patients, 33 patients with oral premalignant lesions divided into 21 oral lichen planus patients and 12 patients with leukoplakia and 30 normal individuals who acted as controls. Oral rinse was collected from all participants and they all underwent conventional visual and tactile examination, and patients with oral lesions had the diagnosis confirmed by histopathological examination of tissue biopsy. DNA integrity index was determined as the ratio between ALU247 and ALU115 measured by qPCR.ResultsThere was no statistically significant difference regarding ALU115, ALU247 and DNA integrity index between the three study groups. The index was significantly higher in the oral cancer group than the oral lichen planus patients, while no significant difference was found between the oral cancer and the leukoplakia cases. The DNA integrity index sensitivity, specificity, positive and negative predictive values were 73%, 45%, 55% and 65% respectively.ConclusionsSalivary DNA integrity index showed poor diagnostic abilities in differentiating between the oral cancer and premalignant lesions.
| S-EPMC8254884 | biostudies-literature
Project description:Helicobacter pylori is the strongest risk factor for the development of gastric cancer. Although the specific mechanisms by which this pathogen induces carcinogenesis have not been fully elucidated, high-expression interleukin (IL)-1β alleles are associated with increased gastric cancer risk among H. pylori-infected persons. In addition, loss of matrix metalloproteinase 7 (MMP7) increases mucosal inflammation in mouse models of epithelial injury, and we have shown that gastric inflammation is increased in H. pylori-infected MMP7(-/-) C57BL/6 mice. In this report, we define mechanisms that underpin such responses and extend these results into a genetic model of MMP7 deficiency and gastric cancer. Wild-type (WT) or MMP7(-/-) C57BL/6 mice were challenged with broth alone as an uninfected control or the H. pylori strain PMSS1. All H. pylori-challenged mice were successfully colonized. As expected, H. pylori-infected MMP7(-/-) C57BL/6 mice exhibited a significant increase in gastric inflammation compared with uninfected or infected WT C57BL/6 animals. Loss of MMP7 resulted in M1 macrophage polarization within H. pylori-infected stomachs, as assessed by Luminex technology and immunohistochemistry, and macrophages isolated from infected MMP7-deficient mice expressed significantly higher levels of the M1 macrophage marker IL-1β compared with macrophages isolated from WT mice. To extend these findings into a model of gastric cancer, hypergastrinemic WT INS-GAS or MMP7(-/-) INS-GAS mice were challenged with H. pylori strain PMSS1. Consistent with findings in the C57BL/6 model, H. pylori-infected MMP7-deficient INS-GAS mice exhibited a significant increase in gastric inflammation compared with either uninfected or infected WT INS-GAS mice. In addition, the incidence of gastric hyperplasia and dysplasia was significantly increased in H. pylori-infected MMP7(-/-) INS-GAS mice compared with infected WT INS-GAS mice, and loss of MMP7 promoted M1 macrophage polarization. These results suggest that MMP7 exerts a restrictive role on H. pylori-induced gastric injury and the development of premalignant lesions by suppressing M1 macrophage polarization.
| S-EPMC4237684 | biostudies-literature
Project description:Oral squamous cell carcinoma (OSCC) is a major cause of cancer-associated morbidity and mortality and may develop from oral premalignant lesions (OPL). An improved molecular classification of OPL may help refining prevention strategies. We identified two main OPL gene-expression subtypes, named immunological and classical, in 86 OPL (discovery dataset). A gene expression-based score was then developed to classify OPL samples from three independent datasets, including 17 (GSE30784),13 (GSE10174) and 15 (GSE85195) OPLs, into either one of the two gene-expression subtypes. Using the single sample gene set enrichment analysis, enrichment scores for immune-related pathways were different between the two OPL subtypes. In OPL from the discovery set, loss of heterozygosities (LOH) at 3p14, 17p13, TP53, 9p21 and 8p22 and miRNA gene expression profiles were analyzed. Deconvolution of the immune infiltrate was performed using the Microenvironment Cell Populations-counter tool. A multivariate analysis revealed that decreased miRNA-142-5p expression (P = 0.0484) and lower T-cell, monocytic and myeloid dendritic cells (MDC) immune infiltration (T-cells, P = 0.0196; CD8 T cells, P = 0.0129; MDC, P = 0.0481; and monocytes, P = 0.0212) were associated with oral cancer development in the immunological subtype only. In contrast, LOH at 3p14 (P = 0.0241), 17p13 (P = 0.0348) and TP53 (P = 0.004) were associated with oral cancer development in the classical subtype only. In conclusion, we identified 2 subtypes of OPLs, namely immune and classical, which may benefit from different and specific personalized prevention interventions.
| S-EPMC6279331 | biostudies-literature
Project description:Macrophages play a central role in immunological responses to metallic species associated with the localized corrosion of metallic implants, and mediating in peri-implant inflammations. Herein, the pathways of localized corrosion-macrophage interactions were systematically investigated on 316L stainless steel (SS) implant metals. Electrochemical monitoring under macrophage-mediated inflammatory conditions showed a decreased pitting corrosion resistance of 316L SSs in the presence of RAW264.7 cells as the cells would disrupt biomolecule adsorbed layer on the metal surface. The pitting potentials were furtherly decreased when the RAW264.7 cells were induced to the M1 pro-inflammatory phenotype by the addition of lipopolysaccharide (LPS), and pitting corrosion preferentially initiated at the peripheries of macrophages. The overproduction of aggressive ROS under inflammatory conditions would accelerate the localized corrosion of 316L SS around macrophages. Under pitting corrosion condition, the viability and pro-inflammatory polarization of RAW264.7 cells were region-dependent, lower viability and more remarkable morphology transformation of macrophages in the pitting corrosion region than the pitting-free region. The pitting corrosion of 316L SS induced high expression of CD86, TNF-α, IL-6 and high level of intracellular ROS in macrophages. Uneven release of metallic species (Fe2+, Cr3+, Ni2+, etc) and uneven distribution of surface overpotential stimulated macrophage inflammatory responses near the corrosion pits. A synergetic effect of localized corrosion and macrophages was revealed, which could furtherly promote localized corrosion of 316L SS and macrophage inflammatory reactions. Our results provided direct evidence of corrosion-macrophage interaction in metallic implants and disclosed the pathways of this mutual stimulation effect. Graphical abstract Image 1 Highlights • Macrophages decreased pitting corrosion resistance of 316 L stainless steel.• Pitting corrosion mediated region-dependent macrophage behavior.• Corrosion-inflammation interaction pathways were revealed.
| S-EPMC10474585 | biostudies-literature
Project description:The chronic inflammation of tumor continues to recruit TAMs (tumor-associated macrophages) to the TME (tumor microenvironment) and promote polarization. Pro-inflammatory signals polarize macrophages to the M1 phenotype to enhance inflammation against pathogens. Tumor inflammatory development changes the pro-inflammatory response to an anti-inflammatory response, resulting in the alteration of macrophages from M1 to M2 to promote tumor progression. Additionally, hypoxia activates HIF (hypoxia-inducible factors) in the TME, which reprograms macrophages to the M2 phenotype to support tumor development. Here, we discuss the factors that drive phenotypic changes in TAMs in the inflammatory TME, which will help in the development of cancer immunotherapy of macrophages.
| S-EPMC9934926 | biostudies-literature
Project description:Transcriptional profiling of hyperplastic, metaplastic, and dysplastic lesions of the bronchus in comparison with normal bronchial epithelium. The aim was to identify transcripts and cell signalling pathways associated with the development of isolated premalignant lesions and/or lesions combined with each other in the same bronchial epithelium.
2016-05-25 | GSE81819 | GEO
Project description:Rationale: The clinical treatment of epilepsy is faced with challenges. On the one hand, the effectiveness of existing antiepileptic drugs (AEDs) is limited by the blood‒brain barrier (BBB); on the other hand, changes in the inflammatory microenvironment during epileptogenesis are often neglected. Methods: The death-associated protein kinase 1 inhibitor TC-DAPK6 and the fluorescent probe rhodamine B were encapsulated in hollow mesoporous silica nanocarriers (HMSNs), which were then coated with a macrophage membrane to prepare macrophage membrane-biomimetic nanoparticles, namely, MA@RT-HMSNs. In vitro biotoxicity, cellular uptake, BBB permeability and inflammatory targeting ability were evaluated in cells. The effects of MA@RT-HMSN treatment were explored by immunohistochemistry, TUNEL assay, Western blot analysis, quantitative real-time polymerase chain reaction, electroencephalogram recording and behavioural tests in kainic acid-induced acute and chronic epilepsy model mice. Results: MA@RT-HMSNs showed excellent biocompatibility both in vitro and in vivo. MA@RT-HMSNs successfully crossed the BBB and exhibited increased efficacy in targeted delivery of TC-DAPK6 to inflammatory lesions in epileptic foci. Macrophage membrane coating conferred MA@RT-HMSNs with higher stability, greater cellular uptake, and enhanced TC-DAPK6 bioavailability. Furthermore, MA@RT-HMSNs exerted beneficial therapeutic effects on acute and chronic epilepsy models by alleviating microenvironment inflammation, preventing neuronal death, and inhibiting neuronal excitability and gliosis. Conclusions: MA@RT-HMSNs target inflammatory foci to inhibit death-related protein kinase 1 and exert antiepileptic effects. This study provides a promising biomimetic nanodelivery system for targeted epilepsy therapy.
| S-EPMC11519803 | biostudies-literature
Project description:Oral cancers are attributed to a number of causal agents including tobacco, alcohol, human papillomavirus (HPV), and areca (betel) nut. Although betel nut chewing has been established as an independent cause of oral cancer, the mechanisms of carcinogenesis are poorly understood. An investigation was undertaken to evaluate the influence of betel nut chewing on the oral microbiome and oral premalignant lesions. Study participants were recruited from a dental clinic in Guam. Structured interviews and oral examinations were performed. Oral swabbing and saliva samples were evaluated by 454 pyrosequencing of the V3- V5 region of the 16S rRNA bacterial gene and genotyped for HPV. One hundred twenty-two adults were enrolled including 64 current betel nut chewers, 37 former chewers, and 21 with no history of betel nut use. Oral premalignant lesions, including leukoplakia and submucous fibrosis, were observed in 10 chewers. Within-sample bacterial diversity was significantly lower in long-term (≥10 years) chewers vs. never chewers and in current chewers with oral lesions vs. individuals without lesions. Between-sample bacterial diversity based on Unifrac distances significantly differed by chewing status and oral lesion status. Current chewers had significantly elevated levels of Streptococcus infantis and higher and lower levels of distinct taxa of the Actinomyces and Streptococcus genera. Long-term chewers had reduced levels of Parascardovia and Streptococcus. Chewers with oral lesions had significantly elevated levels of Oribacterium, Actinomyces, and Streptococcus, including Streptococcus anginosus. In multivariate analyses, controlling for smoking, oral HPV, S.anginosus, and S. infantis levels, current betel nut chewing remained the only predictor of oral premalignant lesions. Our study provides evidence that betel nut chewing alters the oral bacterial microbiome including that of chewers who develop oral premalignant lesions. Nonetheless, whether microbial changes are involved in betel nut-induced oral carcinogenesis is only speculative. Further research is needed to discern the clinical significance of an altered oral microbiome and the mechanisms of oral cancer development in betel nut chewers.
| S-EPMC5321455 | biostudies-literature