Elucidating the molecular and immune interplay between head and neck squamous cell carcinoma and diffuse large B-cell lymphoma through bioinformatics and machine learning DOI Open Access

Jing Zheng,

Xinxin Li, Xun Gong

et al.

Translational Cancer Research, Journal Year: 2024, Volume and Issue: 13(11), P. 5725 - 5750

Published: Nov. 1, 2024

Head and neck squamous cell carcinoma (HNSCC) contributes significantly to global health challenges, presenting primarily in the oral cavity, pharynx, nasopharynx, larynx. HNSCC has a high propensity for lymphatic metastasis. Diffuse large B-cell lymphoma (DLBCL), most common subtype of non-Hodgkin lymphoma, exhibits significant heterogeneity aggressive behavior, leading mortality rates. Epstein-Barr virus (EBV) is notably associated with DLBCL certain types HNSCC. The purpose this study elucidate molecular immune interplay between using bioinformatics machine learning (ML) identify shared biomarkers potential therapeutic targets. Differentially expressed genes (DEGs) were identified "limma" package R from dataset Cancer Genome Atlas (TCGA) database, relevant modules selected through weighted gene co-expression network analysis (WGCNA) Gene Expression Omnibus (GEO) database. Based on their intersection genes, functional enrichment analyses conducted Ontology (GO), Disease Ontology, Kyoto Encyclopedia Genes Genomes (KEGG) databases. Protein-protein interaction (PPI) networks ML algorithms employed screen biomarkers. prognostic value these was evaluated Kaplan-Meier (K-M) survival receiver operating characteristic (ROC) curve analyses. Human Protein (HPA) database facilitated examination messenger RNA (mRNA) protein expressions. Further mutations, infiltration, drug predictions, pan-cancer impacts performed. Additionally, single-cell sequencing (scRNA-seq) data at type level provide deeper insights into tumor microenvironment. From 2,040 DEGs 1,983 module-related 85 identified. PPI six proposed 21 prospective followed yielded 16 candidates. Survival ROC pinpointed four hub genes-ACACB, MMP8, PAX5, TNFAIP6-as patient outcomes, demonstrating predictive capabilities. Evaluations mutations coupled prediction comprehensive cancer analysis, highlighted biomarkers' roles response treatment efficacy. scRNA-seq revealed an increased abundance fibroblasts, epithelial cells mononuclear phagocyte system (MPs) tissues compared lymphoid tissues. MMP8 showed higher expression five tissues, while TNFAIP6 PAX5 exhibited specific types. Leveraging ML, pivotal diagnostic capabilities corroborates accuracy, supporting development nomogram assist clinical decision-making.

Language: Английский

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

Citations

12
Targeting neutrophils: Mechanism and advances in cancer therapy DOI Creative Commons
Shuaixi Yang,

Jiachi Jia,

Fuqi Wang

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(3)

Published: March 1, 2024

Abstract Background Cancer is a thorny problem which cannot be conquered by mankind at present and recent researchers have put their focus on tumor microenviroment. Neutrophils, the prominent leukocytes in peripheral blood that accumulate tumours, serves as frontline cells response to tumour progression owing rapid development of micro biotechnology. Hence, targeted therapy with these neutrophils has made targeting treatment promising field cancer therapy. Main body We broadly summarise some studies phenotypes functions tumour‐associated well unique web‐like products play role progression—neutrophil extracellular traps—and interactions between microenvironment. Moreover, several therapeutic progress provided potential strategies for cancer. Conclusion This review aims offer holistic perspective interventions further inspire more researches therapies.

Language: Английский

Citations

15
Neutrophil extracellular traps in cancer DOI Creative Commons
Yuxi Ma, Jielin Wei, Wenshan He

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 15, 2024

Neutrophil extracellular traps (NETs), which consist of chromatin DNA studded with granule proteins, are released by neutrophils in response to both infectious and sterile inflammation. Beyond the canonical role defense against pathogens, extrusion NETs also contributes initiation, metastasis, therapeutic malignant diseases. Recently, have been implicated development responses various types tumors. Although extensive work regarding inflammation tumors has reported, a comprehensive summary how these web-like structures initiate propagate tumor progression under specific microenvironment is lacking. In this review, we demonstrate initiators related signaling pathways that trigger formation cancers. Additionally, review will outline current molecular mechanisms regulatory networks during dormant cancer cells awakening, circulating (CTCs) extravasation, metastatic recurrence cancer. This followed perspective on potential clinical as targets treatment local disease, including improvement efficacy existing therapies.

Language: Английский

Citations

10
Neutrophil diversity and function in health and disease DOI Creative Commons

F Zhang,

Yidan Xia,

Jiayang Su

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Dec. 5, 2024

Abstract Neutrophils, the most abundant type of granulocyte, are widely recognized as one pivotal contributors to acute inflammatory response. Initially, neutrophils were considered mobile infantry innate immune system, tasked with immediate response invading pathogens. However, recent studies have demonstrated that versatile cells, capable regulating various biological processes and impacting both human health disease. Cytokines other active mediators regulate functional activity by activating multiple receptors on these thereby initiating downstream signal transduction pathways. Dysfunctions in disruptions neutrophil homeostasis been implicated pathogenesis numerous diseases, including cancer disorders, often due aberrant intracellular signaling. This review provides a comprehensive synthesis functions, integrating advancements this field. Moreover, it examines roles signaling pathways involved regulation activity. The pathophysiology diseases emerging therapeutic approaches targeting them also elaborated. addresses current limitations within field research, highlighting critical gaps knowledge warrant further investigation. In summary, seeks establish multidimensional model regulation, providing new perspectives for potential clinical applications research.

Language: Английский

Citations

6
Tumor Microenvironment: Cellular Interaction and Metabolic Adaptations DOI Open Access
Monica Benvenuto, Chiara Focaccetti

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3642 - 3642

Published: March 25, 2024

The tumor microenvironment (TME) plays a critical role in cancerogenesis [...]

Language: Английский

Citations

4
Tumor-infiltrating myeloid cells; mechanisms, functional significance, and targeting in cancer therapy DOI Creative Commons
Fatemeh Sadat Toghraie, Maryam Bayat, Mahsa Sadat Hosseini

et al.

Cellular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Tumor-infiltrating myeloid cells (TIMs), which encompass tumor-associated macrophages (TAMs), neutrophils (TANs), myeloid-derived suppressor (MDSCs), and dendritic (TADCs), are of great importance in tumor microenvironment (TME) integral to both pro- anti-tumor immunity. Nevertheless, the phenotypic heterogeneity functional plasticity TIMs have posed challenges fully understanding their complexity roles within TME. Emerging evidence suggested that presence is frequently linked prevention cancer treatment improvement patient outcomes survival. Given pivotal function TME, recently been recognized as critical targets for therapeutic approaches aimed at augmenting immunostimulatory cell populations while depleting or modifying those immunosuppressive. This review will explore important properties related immunity, angiogenesis, metastasis. We also document latest strategies targeting preclinical clinical settings. Our objective illustrate potential immunological may improve existing treatments.

Language: Английский

Citations

0
FN1 Immunoregulation in Glioblastoma: Insights From Neutrophil‐Centric Studies DOI Creative Commons
Xiangtian Meng, Xiaoming Yang,

Junle Zhu

et al.

Cancer Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Neutrophils, as key components of the tumor microenvironment, play a crucial role in cancer progression and prognosis. This study aimed to identify neutrophil-related gene signature improve prognostic predictions explore potential immunotherapy targets for glioblastoma multiforme (GBM) patients. Through co-expression analysis, 60 neutrophil-associated genes were identified, showing significant enrichment 159 Gene Ontology terms eight KEGG pathways. Among these, 10 significantly associated with patient survival, leading development six-gene risk model termed Neutrophil-Related Prognostic Index (NRGPI). The NRGPI predicted overall survival (OS) both training validation cohorts (p < 0.05), enhanced accuracy when combined clinicopathological factors. Higher scores correlated worse OS, increased mortality, more aggressive disease progression. Immune profiling linked immune cell infiltration, checkpoint expression, mutation burden, suggesting its identifying candidates immunotherapy. identified genes, FN1 emerged central regulator, composition poor Pan-cancer analysis revealed consistent upregulation across types, underscoring broad clinical relevance. Additionally, tissue microarray using multiplex immunofluorescence on 84 GBM samples confirmed FN1, SDC1, TWIST1, higher levels reduced survival. These findings establish valuable biomarker GBM, offering novel insights into landscape positioning promising therapeutic target further investigation treatment.

Language: Английский

Citations

0
Decoding STING’s roles in cancer: immunity, pain, dormancy, and autophagy DOI
Huan‐Xin Lin, Ya‐ling Tang,

Xinhua Liang

et al.

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Language: Английский

Citations

0
Targeting the Senescent Tumor Microenvironment to Sensitize Immunotherapy DOI
Wen Sun

Highlights in Science Engineering and Technology, Journal Year: 2025, Volume and Issue: 139, P. 260 - 271

Published: April 28, 2025

The tumor microenvironment (TME) plays a pivotal role in cancer progression, metastasis, and therapeutic resistance. Cellular senescence within the TME, characterized by irreversible growth arrest senescence-associated secretory phenotype (SASP), profoundly impacts biology immunotherapy efficacy. senescent TME promotes growth, invasion, metastasis through complex interactions between cells, SASP factors, extracellular matrix (ECM). Simultaneously, senescence-induced alterations immune cell function, including T exhaustion, macrophage polarization, impaired natural killer (NK) cytotoxicity, contribute to an immunosuppressive niche that hinders immunosurveillance fosters evasion. Mounting evidence suggests is critical mediator of resistance checkpoint inhibitors (ICIs). Senescence-associated changes dampen antitumor immunity reducing CD8+ infiltration functionality while promoting accumulation populations such as regulatory cells (Tregs) myeloid-derived suppressor (MDSCs). Consequently, strategies targeting have emerged promising approaches enhance ICI Senolytic agents, inhibitors, combinatorial therapies aimed at eliminating modulating SASP, reprogramming shown potential preclinical models sensitize tumors immunotherapy. As our understanding evolves, it becoming increasingly clear multifaceted approach integrating TME-targeted interventions with necessary overcome improve patient outcomes. Future research should focus on elucidating molecular mechanisms underlying senescence-driven resistance, identifying robust biomarkers predict treatment response, developing novel synergize ICIs. By harnessing approaches, we can expand scope efficacy immunotherapy, ultimately leading improved survival quality life for patients.

Language: Английский

Citations

0
Knowledge landscape of tumor-associated neutrophil: a bibliometric and visual analysis from 2000-2024 DOI Creative Commons

Chaoyue Xiao,

Xiang Feng,

Wufuer Aini

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 4, 2024

Background Neutrophils have long been consistently adjudged to hold a dominant position in acute inflammation, which once led people undervalue their role chronic malignancy. It is now acknowledged that neutrophils also infiltrate into the tumor microenvironment substantial quantities and form highly abundant immune population within tumor, known as tumor-associated (TANs). There has surge of interest researching eminent heterogeneity plasticity TANs recent years, scholars increasingly cotton on multifaceted functions so strenuous endeavors devoted enunciating potential therapeutic targets. Yet it remains much left translate TAN-targeted immunotherapies clinical practice. Therefore, there great significance comprehensively appraise research status, focal point, evolution trend TAN by using bibliometric analysis. Methods Publications related from 2000 2024 are extracted Web Science Core Collection. Bibliometric analysis visualization were performed tools encompassing Microsoft Excel, VOSviewer, CiteSpace, R-bibliometrix, on. Results The included total 788 publications authored 5291 affiliated with 1000 institutions across 58 countries/regions, relevant articles published 324 journals. Despite China’s maximum quantity top 10 institutions, United States leading country most high-quality global cooperation center. FRONTIERS IN IMMUNOLOGY papers, whereas CANCER RESEARCH highest co-cited journal. Israeli professor Fridlender, Zvi G. founder, pioneer, cultivator citation counts H-index area. Our prefigures future trajectories: heterogeneity, neutrophil extracellular trap, crosstalk between immunocytes, immunotherapy will likely be focus research. Conclusion A comprehensive visual first map current landscape intellectual structure TAN, proffers fresh perspectives for further accurate identification distinct subpopulations precise targeting key pro-tumor/anti-tumor immense develop immunotherapy.

Language: Английский

Citations

1