Cancer stem cells and tumor-associated macrophages as mates in tumor progression: mechanisms of crosstalk and advanced bioinformatic tools to dissect their phenotypes and interaction

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 6, 2025

Cancer stem cells (CSCs) are a small subset within the tumor mass significantly contributing to cancer progression through dysregulation of various oncogenic pathways, driving growth, chemoresistance and metastasis formation. The aggressive behavior CSCs is guided by several intracellular signaling pathways such as WNT, NF-kappa-B, NOTCH, Hedgehog, JAK-STAT, PI3K/AKT1/MTOR, TGF/SMAD, PPAR MAPK kinases, well extracellular vesicles exosomes, molecules cytokines, chemokines, pro-angiogenetic growth factors, which finely regulate CSC phenotype. In this scenario, microenvironment (TME) key player in establishment permissive niche, where engage intricate communications with diverse immune cells. "oncogenic" mainly represented B T lymphocytes, NK cells, dendritic Among macrophages exhibit more plastic adaptable phenotype due their different subpopulations, characterized both immunosuppressive inflammatory phenotypes. Specifically, tumor-associated (TAMs) create an milieu production plethora paracrine factors (IL-6, IL-12, TNF-alpha, TGF-beta, CCL1, CCL18) promoting acquisition stem-like, invasive metastatic TAMs have demonstrated ability communicate via direct ligand/receptor (such CD90/CD11b, LSECtin/BTN3A3, EPHA4/Ephrin) interaction. On other hand, exhibited capacity influence creating favorable for progression. Interestingly, bidirectional TME leads epigenetic reprogramming sustains malignant transformation. Nowadays, integration biological computational data obtained cutting-edge technologies (single-cell RNA sequencing, spatial transcriptomics, trajectory analysis) has improved comprehension biunivocal multicellular dialogue, providing comprehensive view heterogeneity dynamics CSCs, uncovering alternative mechanisms evasion therapeutic resistance. Moreover, combination biology will lead development innovative target therapies dampening CSC-TME Here, we aim elucidate most recent insights on complex interactions specifically TAMs, tracing exhaustive scenario from primary

Language: Английский

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Fusion genes in pancreatic tumors

Trends in cancer, Journal Year: 2024, Volume and Issue: 10(5), P. 430 - 443

Published: Feb. 19, 2024

Gene fusions and rearrangements play a crucial role in tumor biology. They are rare events typically detected KRAS wild-type (WT) pancreatic tumors. Their identification can inform clinical management by enabling precision oncology, as involving BRAF, FGFR2, RET, NTRK, NRG1, ALK represent actionable targets KRAS-WT cancers, serve diagnostic purposes since PRKACA/B the hallmark of intraductal oncocytic papillary neoplasms (IOPNs). Although they rare, therapeutic importance these genomic should not be underestimated, highlighting need for quality-ensured molecular diagnostics cancer. Herein we review existing literature on fusion genes tumors their potential effective biomarkers targets.

Language: Английский

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UBE2J1 is identified as a novel plasma cell-related gene involved in the prognosis of high-grade serous ovarian cancer

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 28, 2025

Immune cells within tumor tissues play important roles in remodeling the microenvironment, thus affecting progression and therapeutic response. The current study was designed to identify key markers of plasma explore their role high-grade serous ovarian cancer (HGSOC). We utilized single-cell sequencing data from Gene Expression Omnibus (GEO) database immune cell types HGSOC extract related via Seurat package. effects on prognosis were analyzed univariate Cox regression, least absolute shrinkage selection operator (LASSO) gene set variation analysis (GSVA) bulk Cancer Genome Atlas (TCGA)-HGSOC cohort. Finally, evaluated Cell Counting Kit-8 (CCK-8), Transwell, colony formation, wound healing, immunofluorescence vivo growth assays. At level, we detected a significant increase proportion samples compared that normal samples. Within tissues, these found interact with CD8 + T cells, fibroblasts endothelial cells. In addition, patients high-plasma cell-related score group had better survival rates higher epithelial‒mesenchymal transition (EMT), apoptosis scores. Moreover, LASSO regression analyses revealed ubiquitin-conjugating enzyme E2 J1 (UBE2J1) is prognostic marker HGSOC. Further functional studies overexpression UBE2J1 promoted proliferation, invasion, migration whereas knockdown attenuated abovementioned cellular behaviors. Additionally, EMT, as evidenced by alterations protein expression levels N-cadherin, snail family transcriptional repressor 2 (Slug), Twist BHLH transcription factor 1 (Twist 1) E-cadherin. silencing able inhibit vivo. Overall, this elucidated novel oncogene HGSOC, uncovering new mechanisms tumorigenesis promising targets for patients.

Language: Английский

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Spatial multi-omics analysis of tumor-stroma boundary cell features for predicting breast cancer progression and therapy response

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 26, 2025

Background The tumor boundary of breast cancer represents a highly heterogeneous region. In this area, the interactions between malignant and non-malignant cells influence progression, immune evasion, drug resistance. However, spatial transcriptional profile its role in prognosis treatment response remain unclear. Method Utilizing Cottrazm algorithm, we reconstructed intricate boundaries identified differentially expressed genes (DEGs) associated with these regions. Cell-cell co-positioning analysis was conducted using SpaCET, which revealed key tumor-associated macrophage (TAMs) cancer-associated fibroblasts (CAFs). Additionally, Lasso regression employed to develop body signature (MBS), subsequently validated TCGA dataset for prediction assessment. Results Our research indicates that is characterized by rich reconstruction extracellular matrix (ECM), immunomodulatory regulation, epithelial-to-mesenchymal transition (EMT), underscoring significance progression. Spatial colocalization reveals significant interaction CAFs M2-like (TAM), contributes exclusion MBS score effectively stratifies patients into high-risk groups, survival outcomes exhibiting high scores being significantly poorer. Furthermore, sensitivity demonstrates high-MB tumors had poor chemotherapy strategies, highlighting modulating therapeutic efficacy. Conclusion Collectively, investigate transcription group bulk data elucidate characteristics molecules cancer. CAF-M2 phenotype emerges as critical determinant immunosuppression resistance, suggesting targeting may improve responses. serves novel prognostic tool offers potential strategies guiding personalized approaches

Language: Английский

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Exosomal circular RNAs in tumor microenvironment: An emphasis on signaling pathways and clinical opportunities

MedComm, Journal Year: 2024, Volume and Issue: 5(12)

Published: Nov. 24, 2024

Exosomes can regulate the malignant progression of tumors by carrying a variety genetic information and transmitting it to target cells. Recent studies indicate that exosomal circular RNAs (circRNAs) multiple biological processes in carcinogenesis, such as tumor growth, metastasis, epithelial-mesenchymal transition, drug resistance, autophagy, metabolism, angiogenesis, immune escape. In microenvironment (TME), circRNAs be transferred among cells, endothelial cancer-associated fibroblasts, microbiota, affecting initiation progression. Due high stability widespread presence circRNAs, they hold promise biomarkers for diagnosis prognosis prediction blood urine. addition, designing nanoparticles targeting utilizing derived from cells or stem provide new strategies cancer therapy. this review, we examined crucial role regulating tumor-related signaling pathways summarized transmission between various types their impact on TME. Finally, our review highlights potential diagnostic prognostic biomarkers, well suggesting clinical

Language: Английский

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Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 71 - 71

Published: Jan. 6, 2025

The tumor microenvironment (TME) plays a pivotal role in neoplastic initiation and progression. Epigenetic machinery, governing the expression of core oncogenes suppressor genes transformed cells, significantly contributes to development at both primary distant sites. Recent studies have illuminated how epigenetic mechanisms integrate external cues downstream signals, altering phenotype stromal cells immune cells. This remolds area surrounding ultimately fostering an immunosuppressive microenvironment. Therefore, correcting TME by targeting modifications holds substantial promise for cancer treatment. review synthesizes recent research that elucidates impact specific regulations-ranging from DNA methylation histone chromatin remodeling-on within TME. Notably, we highlight their functional roles either promoting or restricting We also discuss potential applications agents treatment, envisaging ability normalize ecosystem. aims assist researchers understanding dynamic interplay between epigenetics TME, paving way better therapy.

Language: Английский

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Revealing the prognostic potential of natural killer cell-related genes in hepatocellular carcinoma: the key role of NRAS

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 18, 2025

Hepatocellular carcinoma (HCC) is a common malignancy associated with high morbidity and mortality rates worldwide. To improve the prognosis of HCC, early diagnosis crucial. However, to date, little known about role natural killer cell-related genes (NKCRGs) in predicting hepatocellular patients. In this study, we identified 24 differentially expressed NKCRGs HCC specimens from TCGA dataset, including 22 upregulated 2 downregulated genes. Functional enrichment analysis revealed that these were mainly involved immune response pathways various cancer-related pathways. Univariate 21 prognostic NKCRGs, eight (PAK1, MAP2K2, MAPK3, PLCG1, SHC1, HRAS, NRAS, MICB) confirmed be through Venn diagram analysis. A model was developed using LASSO-Cox regression, incorporating four (MAP2K2, NRAS). The model's risk score significantly overall survival (OS) both ICGC cohorts. Patients high-risk scores had poorer OS, as demonstrated by Kaplan-Meier curves ROC analyses. not correlated gender or age but higher patients advanced tumor grades stages. Immune status ssGSEA showed for cells group. Additionally, positively score, indicating its potential microenvironment modulation. Expression NRAS tissues, expressions shorter OS. Knockdown experiments silencing suppressed proliferation cells, highlighting therapeutic target. Overall, our findings suggest particularly play crucial roles progression could serve valuable markers targets.

Language: Английский

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Bridging tissue repair and epithelial carcinogenesis: epigenetic memory and field cancerization

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 16, 2024

Language: Английский

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Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12848 - 12848

Published: Nov. 29, 2024

This review explores some of the complex mechanisms underlying antitumor T-cell response, with a specific focus on balance and cross-talk between selected co-stimulatory inhibitory pathways. The tumor microenvironment (TME) fosters both activation exhaustion, dual role influenced by local presence immune checkpoints (ICs), which are exploited cancer cells to evade surveillance. Recent advancements in IC blockade (ICB) therapies have transformed treatment. However, only fraction patients respond favorably, highlighting need for predictive biomarkers combination overcome ICB resistance. A crucial aspect is represented complexity TME, encompasses diverse cell types that either enhance or suppress responses. underscores importance identifying most critical molecules developing approaches tailored patient-specific molecular profiles maximize therapeutic efficacy inhibitors clinical outcomes.

Language: Английский

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Follicular lymphoma research: an open dialogue for a collaborative roadmap

Histopathology, Journal Year: 2024, Volume and Issue: 86(1), P. 79 - 93

Published: Oct. 29, 2024

Follicular lymphoma (FL) is the second most common type of (20% all non-Hodgkin lymphomas), derived from germinal centre (GC) B cells, and characterised by its significant clinical, prognostic biological heterogeneity, leading to complexity in management. Despite investigation indisputable clinical progress since advent immunotherapy era more than 20 years ago, much remains be done understand cure this lymphoma. Today, FL metaphorically a giant puzzle on table with patches sky, landscape foliage clearly appearing. However, many remaining pieces are held various stakeholders (e.g. clinicians, pathologists, researchers, drug developers) without global agreement what gaps are, or any clear blueprint how solve understanding heterogeneity disease create curative tailored therapies. With new technologies, together recent advances our capacity manage big data, time seems ripe for change scale. More ever, will require collaboration between within overcome current bottlenecks field. As every investigator, we acknowledge that first draft necessarily biased, incomplete some expert readers might recognise not addressed. We hope they reply make effort collaborative one assemble ideal fashion. such, review intends step an interactive platform roadmap towards better care FL.

Language: Английский

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