Complex Communication Networks Research Articles

Exploring the interplay between triple-negative breast cancer stem cells and tumor microenvironment for effective therapeutic strategies.

Triple-negative breast cancer (TNBC)is a highly aggressive and metastatic malignancy with poor treatment outcomes. The interaction between the tumor microenvironment (TME)and breast cancer stem cells (BCSCs)plays an important role in the development of TNBC. Owing to their ability of self-renewal and multidirectional differentiation, BCSCs maintain tumor growth, drive metastatic colonization, and facilitate the development of drug resistance. TME is the main factor regulating the phenotype and metastasis of BCSCs. Immune cells, cancer-related fibroblasts (CAFs),cytokines, mesenchymal cells, endothelial cells, and extracellular matrix within the TME form a complex communication network, exert highly selective pressure on the tumor, and provide a conducive environment for the formation of BCSC niches. Tumor growth and metastasis can be controlled by targeting the TME to eliminate BCSC niches or targeting BCSCs to modify the TME. These approaches may improve the treatment outcomes and possess great application potential in clinical settings. In this review, we summarized the relationship between BCSCs and the progression and drug resistance of TNBC, especially focusing on the interaction between BCSCs and TME. In addition, we discussed therapeutic strategies that target the TME to inhibit or eliminate BCSCs, providing valuable insights into the clinical treatment of TNBC.

New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication.

Cancer is one of the leading causes of death worldwide, and more effective ways of attacking cancer are being sought. Cancer immunotherapy is a new and effective therapeutic method after surgery, radiotherapy, chemotherapy, and targeted therapy. Cancer immunotherapy aims to kill tumor cells by stimulating or rebuilding the body's immune system, with specific efficiency and high safety. However, only few tumor patients respond to immunotherapy and due to the complex and variable characters of cancer immune escape, the behavior and regulatory mechanisms of immune cells need to be deeply explored from more dimensions. Epigenetic modifications, metabolic modulation, and cell-to-cell communication are key factors in immune cell adaptation and response to the complex tumor microenvironment. They collectively determine the state and function of immune cells through modulating gene expression, changing in energy and nutrient demands. In addition, immune cells engage in complex communication networks with other immune components, which are mediated by exosomes, cytokines, and chemokines, and are pivotal in shaping the tumor progression and therapeutic response. Understanding the interactions and combined effects of such multidimensions mechanisms in immune cell modulation is important for revealing the mechanisms of immunotherapy failure and developing new therapeutic targets and strategies.

A nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila

Pancreatic β cells secrete insulin in response to glucose elevation to maintain glucose homeostasis. A complex network of inter-organ communication operates to modulate insulin secretion and regulate glucose levels after a meal. Lipids obtained from diet or generated intracellularly are known to amplify glucose-stimulated insulin secretion, however, the underlying mechanisms are not completely understood. Here, we show that a Drosophila secretory lipase, Vaha (CG8093), is synthesized in the midgut and moves to the brain where it concentrates in the insulin-producing cells in a process requiring Lipid Transfer Particle, a lipoprotein originating in the fat body. In response to dietary fat, Vaha stimulates insulin-like peptide release (ILP), and Vaha deficiency results in reduced circulatory ILP and diabetic features including hyperglycemia and hyperlipidemia. Our findings suggest Vaha functions as a diacylglycerol lipase physiologically, by being a molecular link between dietary fat and lipid amplified insulin secretion in a gut-brain axis.

DNA Reaction Circuits to Establish Designated Biological Functions in Multicellular Community.

In multicellular organisms, individual cells are coordinated through complex communication networks to accomplish various physiological tasks. Aiming to establish new biological functions in the multicellular community, we used DNA as the building block to develop a cascade of nongenetic reaction circuits to establish a dynamic cell-cell communication network. Utilizing membrane-anchored amphiphilic DNA tetrahedra (TDN) as the nanoscaffold, reaction circuits were incorporated into three unrelated cells in order to uniquely regulate their sense-and-response behaviors. As a proof-of-concept, this step enabled these cells to simulate significant biological events involved in T cell-mediated anticancer immunity. Such events included cancer-associated antigen recognition and the presentation of antigen-presenting cells (APCs), APC-facilitated T cell activation and dissociation, and T cell-mediated cancer targeting and killing. By combining the excellent programmability and molecular recognition ability of DNA, our cell-surface reaction circuits hold promise for mimicking and manipulating many biological processes.

Single-Cell Informatics for Tumor Microenvironment and Immunotherapy.

Cancer comprises malignant cells surrounded by the tumor microenvironment (TME), a dynamic ecosystem composed of heterogeneous cell populations that exert unique influences on tumor development. The immune community within the TME plays a substantial role in tumorigenesis and tumor evolution. The innate and adaptive immune cells "talk" to the tumor through ligand-receptor interactions and signaling molecules, forming a complex communication network to influence the cellular and molecular basis of cancer. Such intricate intratumoral immune composition and interactions foster the application of immunotherapies, which empower the immune system against cancer to elicit durable long-term responses in cancer patients. Single-cell technologies have allowed for the dissection and characterization of the TME to an unprecedented level, while recent advancements in bioinformatics tools have expanded the horizon and depth of high-dimensional single-cell data analysis. This review will unravel the intertwined networks between malignancy and immunity, explore the utilization of computational tools for a deeper understanding of tumor-immune communications, and discuss the application of these approaches to aid in diagnosis or treatment decision making in the clinical setting, as well as the current challenges faced by the researchers with their potential future improvements.

The Power of Psychobiotics in Depression: A Modern Approach through the Microbiota-Gut-Brain Axis: A Literature Review.

The microbiota-gut-brain (MGB) axis is a complex communication network linking the gut, microbiota, and brain, influencing various aspects of health and disease. Dysbiosis, a disturbance in the gut microbiome equilibrium, can significantly impact the MGB axis, leading to alterations in microbial composition and function. Emerging evidence highlights the connection between microbiota alterations and neurological and psychiatric disorders, including depression. This review explores the potential of psychobiotics in managing depressive disorders, emphasizing their role in restoring microbial balance and influencing the MGB axis. Psychobiotics exhibit positive effects on the intestinal barrier, immune response, cortisol levels, and the hypothalamic-pituitary-adrenal (HPA) axis. Studies suggest that probiotics may serve as an adjunct therapy for depression, especially in treatment-resistant cases. This review discusses key findings from studies on psychobiotics interventions, emphasizing their impact on the gut-brain axis and mental health. The increasing acceptance of the expanded concept of the MGB axis underscores the importance of microorganisms in mental well-being. As our understanding of the microbiome's role in health and disease grows, probiotics emerge as promising agents for addressing mental health issues, providing new avenues for therapeutic interventions in depressive disorders.

Telocytes: current methods of research, challenges and future perspectives.

Telocytes (TCs) are CD34-positive interstitial cells that have long cytoplasmic projections, called telopodes; they have been identified in several organs and in various species. These cells establish a complex communication network between different stromal and epithelial cell types, and there is growing evidence that they play a key role in physiology and pathology. In many tissues, TC network impairment has been implicated in the onset and progression of pathological conditions, which makes the study of TCs of great interest for the development of novel therapies. In this review, we summarise the main methods involved in the characterisation of these cells as well as their inherent difficulties and then discuss the functional assays that are used to uncover the role of TCs in normal and pathological conditions, from the most traditional to the most recent. Furthermore, we provide future perspectives in the study of TCs, especially regarding the establishment of more precise markers, commercial lineages and means for drug delivery and genetic editing that directly target TCs.

Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in choroidal neovascularization model

Choroidal neovascularization (CNV) is a hallmark of neovascular age-related macular degeneration (nAMD) and a major contributor to vision loss in nAMD cases. However, the identification of specific cell types associated with nAMD remains challenging. Herein, we performed single-cell sequencing to comprehensively explore the cellular diversity and understand the foundational components of the retinal pigment epithelium (RPE)/choroid complex. We unveiled 10 distinct cell types within the RPE/choroid complex. Notably, we observed significant heterogeneity within endothelial cells (ECs), fibroblasts, and macrophages, underscoring the intricate nature of the cellular composition in the RPE/choroid complex. Within the EC category, four distinct clusters were identified and EC cluster 0 was tightly associated with choroidal neovascularization. We identified five clusters of fibroblasts actively involved in the pathogenesis of nAMD, influencing fibrotic responses, angiogenic effects, and photoreceptor function. Additionally, three clusters of macrophages were identified, suggesting their potential roles in regulating the progression of nAMD through immunomodulation and inflammation regulation. Through CellChat analysis, we constructed a complex cell-cell communication network, revealing the role of EC clusters in interacting with fibroblasts and macrophages in the context of nAMD. These interactions were found to govern angiogenic effects, fibrotic responses, and inflammatory processes. In summary, this study reveals noteworthy cellular heterogeneity in the RPE/choroid complex and provides valuable insights into the pathogenesis of CNV. These findings will open up potential avenues for deep understanding and targeted therapeutic interventions in nAMD.

Abstract 5514: Crosstalk between prostatic epithelial cells and the tumor microenvironment drives cancer progression and metastasis

Abstract Prostate cancer is a heterogeneous disease with a slow progression and a highly variable clinical outcome. Recent advances in the clinical handling of localized prostate cancers resulted in an almost 100% 10-year survival, but no curative treatment is currently available for metastatic disease. Thus, understanding the molecular mechanisms of progression of primary tumors to metastasis is crucial to develop new therapeutic strategies. While tumorigenesis initiates in prostatic epithelial cells, various cell types, including cancer associated fibroblasts (CAFs), immune and endothelial cells produce extra-cellular matrix and secrete signaling molecules that might contribute to tumor progression. However, the complex communication network driving tumor progression is poorly characterized. As the tumor suppressors PTEN and TP53 are among the most frequently altered genes in prostate cancer, we generated genetically engineered mice with Pten and Trp53 selective inactivation in prostatic epithelial cells at adulthood. Their analysis revealed that they develop precancerous lesions that progress to invasive and metastatic tumors. Spatial transcriptomic and single-cell analyses of Pten- and Trp53-deficient prostatic tumors identified the presence of a cancer cell population exhibiting cell plasticity driven by Jak/Stat3 signaling and induced by CAF-produced IL6. In addition, these tumors exhibit a hypoxic core and an immune infiltrate dominated by neutrophils. Inhibition of the hypoxic signaling reduced immune infiltration in primary tumors and their metastatic potential, but did not induce apoptosis of Pten- and Trp53- deficient epithelial cells, in contrast to those of Pten-deficient tumors. These results underline the importance of the tumor genomic background for therapeutic intervention. Taken together, our work highlights the key role of the tumor microenvironment in driving prostate cancer progression and uncovers new vulnerabilities of this disease. Citation Format: Darya Yanushko, Beatriz German Falcon, Céline Keime, Tao Ye, Christelle Thibault-Carpentier, Daniel Metzger, Gilles Laverny. Crosstalk between prostatic epithelial cells and the tumor microenvironment drives cancer progression and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5514.

Isothermal titration calorimetry and surface plasmon resonance methods to probe protein–protein interactions

Isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) are two commonly used methods to probe biomolecular interactions. ITC can provide information about the binding affinity, stoichiometry, changes in Gibbs free energy, enthalpy, entropy, and heat capacity upon binding. SPR can provide information about the association and dissociation kinetics, binding affinity, and stoichiometry. Both methods can determine the nature of protein–protein interactions and help understand the physicochemical principles underlying complex biochemical pathways and communication networks. This methods article discusses the practical knowledge of how to set up and troubleshoot these two experiments with some examples.

Pyoluteorin regulates the biosynthesis of 2,4-DAPG through the TetR family transcription factor PhlH in Pseudomonas protegens Pf-5.

Soil and rhizosphere bacteria act as a rich source of secondary metabolites, effectively fighting against a diverse array of pathogens. Certain Pseudomonas species harbor biosynthetic gene clusters for producing both pyoluteorin and 2,4-diacetylphloroglucinol (2,4-DAPG), which are polyketides that exhibit highly similar antimicrobial spectrum against bacteria and fungi or oomycete. A complex cross talk exists between pyoluteorin and 2,4-DAPG biosynthesis, and production of 2,4-DAPG was strongly repressed by pyoluteorin, yet the underlying mechanism is still elusive. In this study, we find that the TetR family transcription factor PhlH is involved in the cross talk between pyoluteorin and 2,4-DAPG biosynthesis. PhlH binds to a palindromic sequence within the promoter of phlG (PphlG), which encodes a C-C bond hydrolase responsible for degrading 2,4-DAPG. As a signaling molecule, pyoluteorin disrupts the PhlH-PphlG complex by binding to PhlH, leading to decreased levels of 2,4-DAPG. Proteomics data suggest that pyoluteorin regulates multiple physiological processes including fatty acid biosynthesis and transportation of taurine, siderophore, and amino acids. Our work not only reveals a novel mechanism of cross talk between pyoluteorin and 2,4-DAPG biosynthesis, but also highlights pyoluteorin's role as a messenger in the complex communication network of Pseudomonas.IMPORTANCEAntibiosis serves as a crucial defense mechanism for microbes against invasive bacteria and resource competition. These bacteria typically orchestrate the production of multiple antibiotics in a coordinated fashion, wherein the synthesis of one antibiotic inhibits the generation of another. This strategic coordination allows the bacterium to focus its resources on producing the most advantageous antibiotic under specific circumstances. However, the underlying mechanisms of distinct antibiotic production in bacterial cells remain largely elusive. In this study, we reveal that the TetR family transcription factor PhlH detects the secondary metabolite pyoluteorin and mediates the cross talk between pyoluteorin and 2,4-DAPG biosynthesis in the biocontrol strain Pseudomonas protegens Pf-5. These findings hold promise for future research, potentially informing the manipulation of these systems to enhance the effectiveness of biocontrol agents.

The Arabidopsis Mitochondrial Nucleoid-Associated Protein WHIRLY2 Is Required for a Proper Response to Salt Stress.

In the last years, plant organelles have emerged as central coordinators of responses to internal and external stimuli, which can induce stress. Mitochondria play a fundamental role as stress sensors being part of a complex communication network between the organelles and the nucleus. Among the different environmental stresses, salt stress poses a significant challenge and requires efficient signaling and protective mechanisms. By using the why2 T-DNA insertion mutant and a novel knock-out mutant prepared by CRISPR/Cas9-mediated genome editing, this study revealed that WHIRLY2 is crucial for protecting mitochondrial DNA (mtDNA) integrity during salt stress. Loss-of-function mutants show an enhanced sensitivity to salt stress. The disruption of WHIRLY2 causes the impairment of mtDNA repair that results in the accumulation of aberrant recombination products, coinciding with severe alterations in nucleoid integrity and overall mitochondria morphology besides a compromised redox-dependent response and misregulation of antioxidant enzymes. The results of this study revealed that WHIRLY2-mediated structural features in mitochondria (nucleoid compactness and cristae) are important for an effective response to salt stress.

Reversibility of disturbed pituitary function in pediatric conditions with psychological stressors: implications for clinical practice.

The complex communication network between the central nervous system and the hypothalamic-pituitary axis forms the basis of endocrine functional plasticity, which facilitates adaptation to changing internal and external conditions, but also makes it vulnerable to the negative effects of stressful psychological factors. Herein, clinical conditions such as functional hypothalamic amenorrhea, eating disorders, growth faltering, post-traumatic stress disorder, and pubertal disorders that may emerge during childhood or adolescence, their origin possibly including psychological stressors, are analyzed regarding their genetic susceptibility and reversibility of endocrine function. A discussion on the optimization of therapeutic management defined by managing stress and maximizing the degree and rate of reversibility follows.

CXCL12+ dermal fibroblasts promote neutrophil recruitment and host defense by recognition of IL-17.

The skin provides an essential barrier for host defense through rapid action of multiple resident and recruited cell types, but the complex communication network governing these processes is incompletely understood. To define these cell-cell interactions more clearly, we performed an unbiased network analysis of mouse skin during invasive S. aureus infection and revealed a dominant role for CXCL12+ fibroblast subsets in neutrophil communication. These subsets predominantly reside in the reticular dermis, express adipocyte lineage markers, detect IL-17 and TNFα, and promote robust neutrophil recruitment through NFKBIZ-dependent release of CXCR2 ligands and CXCL12. Targeted deletion of Il17ra in mouse fibroblasts resulted in greatly reduced neutrophil recruitment and increased infection by S. aureus. Analogous human CXCL12+ fibroblast subsets abundantly express neutrophil chemotactic factors in psoriatic skin that are subsequently decreased upon therapeutic targeting of IL-17. These findings show that CXCL12+ dermal immune acting fibroblast subsets play a critical role in cutaneous neutrophil recruitment and host defense.

Abstract WP75: Interprofessional Medical Education in a Stroke Escape Room to Improve Stroke Education and Communication Skills

Purpose: Acute stroke care requires a foundation of clinical knowledge to quickly recognize symptoms and facilitate rapid, safe treatment. Effective care requires a complex network of communication in a stroke response team. Simulation-based training provides a multimodal approach to learning that reinforces clinical knowledge of stroke and affords the opportunity to demonstrate effective communication skills in critical situations. An interprofessional scenario allows all participants to learn about the different roles required for effective care. Methods: Fifty new graduate nurses participated in a pilot model of a traditional didactic session on stroke knowledge, followed by an “escape room” incorporating this knowledge to solve puzzles. The second iteration was expanded to include incoming neurology PGY-2 residents, registered nurses, and pharmacy residents. After the lecture, participants formed teams including equal numbers of all provider roles. The teams were tasked to complete a timed version of the escape room by solving stroke-based puzzles. The escape room was followed by a debrief of communication skills modeled by TeamSTEPPS. Finally, the same teams were exposed to a simulated “stroke code," which included a focused assessment, interpretation of labs and imaging, and management of barriers to treatment with an end goal of collectively managing a suspected stroke. Results: A 5-point scale was used to assess level of comfort with leadership in initial stroke assessment, management, treatment, and communicating concerns. The average increase in numeric level of comfort was 0.9 (range 0.6 - 1.4). The benefit did appear greater for incoming neurology PGY-2 residents (average increase 1.3, range 0.6 - 1.6) compared to registered nurses (average increase 0.45, range 0.25 to 0.75). Conclusions: Use of an escape room during training for incoming neurology PGY-2 residents, registered nurses, and pharmacy residents provided a novel opportunity to facilitate application of clinical knowledge, leadership, teamwork, shared decision-making, and prioritization of patient safety. Providing interactive sessions in between didactic instruction increased participant engagement and level of comfort with roles in a stroke response team.

Valued-inverse dombi fuzzy graphs

Fuzzy graphs as labeled graphs (fuzzy vertex labeling and fuzzy edge labeling) have many applications in real life such as complex networks, coding theory, medical sciences, communication networks, and management sciences. Also, triangular norms as a special class of functions, have many applications in fuzzy set theory, probability and statistics, and other areas. This paper considers the notations of an inverse fuzzy graph and triangular norms to introduce the new type of graphs as valued-inverse Dombi fuzzy graphs. The valued-inverse Dombi fuzzy graphs are a generalization of inverse fuzzy graphs and are dual to Dombi fuzzy graphs. For any given greater than or equal to one real number, we construct a type of Dombi inverse fuzzy graph and investigate some conditions such that the product and union of Dombi inverse fuzzy graphs be a Dombi inverse fuzzy graph.

Macrophage exosomes modified by miR-365-2-5p promoted osteoblast osteogenic differentiation by targeting OLFML1.

In the bone immune microenvironment, immune cells can regulate osteoblasts through a complex communication network. Macrophages play a central role in mediating immune osteogenesis, exosomes derived from them have osteogenic regulation and can be used as carriers in bone tissue engineering. However, there are problems with exosomal therapy alone, such as poor targeting, and the content of loaded molecules cannot reach the therapeutic concentration. In this study, macrophage-derived exosomes modified with miR-365-2-5p were developed to accelerate bone healing. MC3T3-E1 cells were incubated with the culture supernatants of M0, M1 and M2 macrophages, and it was found that the culture medium of M2 macrophages had the most significant effects in contributing to osteogenesis. High-throughput sequencing identified that miR-365-2-5p was significantly expressed in exosomes derived from M2 macrophages. We incubated MC3T3-E1 with exosomes overexpressing or knocking down miR-365-2-5p to examine the biological function of exosome miR-365-2-5p on MC3T3-E1 differentiation. These findings suggested that miR-365-2-5p secreted by exosomes increased the osteogenesis of MC3T3-E1. Moreover, miR-365-2-5p had a direct influence over osteogenesis for MC3T3-E1. Sequencing analysis combined with dual luciferase detection indicated that miR-365-2-5p binded to the 3'-UTR of OLFML1. In summary, exosomes secreted by M2 macrophages targeted OLFML1 through miR-365-2-5p to facilitate osteogenesis.

Construction of a Label-Detection Integrated Visual Probe to Reveal the Double-Edged Sword Principle of Ferroptosis in Liver Injury.

Ferroptosis has been confirmed as a potential mediator and an indicator of the severity of liver injury. Despite the fruitful results, there are still two deficiencies in the research on the association between ferroptosis and liver injury. First, iron ions are usually selected as the target bioanalyte, but its detection based on a fluorescent probe is interfered with by specific chemical reaction mechanisms, leading to low sensitivity and poor physiological stability. Second, more efforts were focused on the harmful effects of ferroptosis on liver injury and less involved in the therapeutic value of ferroptosis for liver injury. Hence, in this work, we proposed a new nonreactive analyte (mitochondrial viscosity) as an analysis marker, which can circumvent the challenges caused by specific reaction mechanisms of iron ions. Meanwhile, we constructed a novel label-detection integrated visual probe (VPF) to explore the feasibility of ferroptosis in the treatment of liver injury. As expected, we not only successfully traced the dynamic changes in mitochondrial viscosity but also visualized the changes in cell morphology during induced and inhibited ferroptosis. Conspicuously, this work revealed that liver injury can be alleviated by regulating ferroptosis, confirming the therapeutic value of ferroptosis in liver injury. In addition, a complex biological communication network between ferroptosis and liver injury was constructed by western blotting, providing an important theoretical mechanism for revealing their double-edged sword relationship. This study not only provides a new strategy for studying the complex relationship between ferroptosis and liver injury but also facilitates the future treatment of liver injury.

Understanding the Gut-Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders.

The gut-brain axis (GBA) is a complex bidirectional communication network connecting the gut and brain. It involves neural, immune, and endocrine communication pathways between the gastrointestinal (GI) tract and the central nervous system (CNS). Perturbations of the GBA have been reported in many neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others, suggesting a possible role in disease pathogenesis. The gut microbiota is a pivotal component of the GBA, and alterations in its composition, known as gut dysbiosis, have been associated with GBA dysfunction and neurodegeneration. The gut microbiota might influence the homeostasis of the CNS by modulating the immune system and, more directly, regulating the production of molecules and metabolites that influence the nervous and endocrine systems, making it a potential therapeutic target. Preclinical trials manipulating microbial composition through dietary intervention, probiotic and prebiotic supplementation, and fecal microbial transplantation (FMT) have provided promising outcomes. However, its clear mechanism is not well understood, and the results are not always consistent. Here, we provide an overview of the major components and communication pathways of the GBA, as well as therapeutic approaches targeting the GBA to ameliorate NDDs.

Multi-Classification and Tree-Based Ensemble Network for the Intrusion Detection System in the Internet of Vehicles.

The Internet of Vehicles(IoV) employs vehicle-to-everything (V2X) technology to establish intricate interconnections among the Internet, the IoT network, and the Vehicle Networks (IVNs), forming a complex vehicle communication network. However, the vehicle communication network is very vulnerable to attacks. The implementation of an intrusion detection system (IDS) emerges as an essential requisite to ensure the security of in-vehicle/inter-vehicle communication in IoV. Within this context, the imbalanced nature of network traffic data and the diversity of network attacks stand as pivotal factors in IDS performance. On the one hand, network traffic data often heavily suffer from data imbalance, which impairs the detection performance. To address this issue, this paper employs a hybrid approach combining the Synthetic Minority Over-sampling Technique (SMOTE) and RandomUnderSampler to achieve a balanced class distribution. On the other hand, the diversity of network attacks constitutes another significant factor contributing to poor intrusion detection model performance. Most current machine learning-based IDSs mainly perform binary classification, while poorly dealing with multiclass classification. This paper proposes an adaptive tree-based ensemble network as the intrusion detection engine for the IDS in IoV. This engine employs a deep-layer structure, wherein diverse ML models are stacked as layers and are interconnected in a cascading manner, which enables accurate and efficient multiclass classification, facilitating the precise identification of diverse network attacks. Moreover, a machine learning-based approach is used for feature selection to reduce feature dimensionality, substantially alleviating the computational overhead. Finally, we evaluate the proposed IDS performance on various cyber-attacks from the in-vehicle and external networks in IoV by using the network intrusion detection dataset CICIDS2017 and the vehicle security dataset Car-Hacking. The experimental results demonstrate remarkable performance, with an F1-score of 0.965 on the CICIDS2017 dataset and an F1-score of 0.9999 on the Car-Hacking dataset. These scores demonstrate that our IDS can achieve efficient and precise multiclass classification. This research provides a valuable reference for ensuring the cybersecurity of IoV.