Dissertations / Theses on the topic 'Prédiction du trafic'
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Rolland, Chloé. "Modèles orientés objet pour une meilleure prédiction du trafic internet." Paris 6, 2008. http://www.theses.fr/2008PA066657.
Full textLegrand, Jean-François. "Prédiction de trafic dans les réseaux de téléphonie mobile par des méthodes statistiques et neuronales." Paris 6, 2003. http://www.theses.fr/2003PA066543.
Full textPham, Duc-Thinh. "Prédiction de trajectoire et avis de résolution de conflits de trafic aérien basée sur l’apprentissage automatique." Thesis, Paris Sciences et Lettres (ComUE), 2019. http://www.theses.fr/2019PSLEP027.
Full textThe increasing in traffic demand has strained air traffic control system and controllers which lead to the need of novel and efficient conflict detection and resolution advisory. In the scope of this thesis, we concentrate on studying challenges in conflict detection and resolution by using machine learning approaches. We have attempted to learn and predict controller behaviors from data using Random Forest. We also propose a novel approach for probabilistic conflict detection by using Heteroscedastic Gaussian Process as predictive models and Bayesian Optimization for probabilistic conflict detection algorithm. Finally, we propose an artificial intelligent agent that is capable of resolving conflicts, in the presence of traffic and uncertainty. The conflict resolution task is formulated as a decision-making problem in large and complex action space, which is applicable for employing reinforcement learning algorithm. Our work includes the development of a learning environment, scenario state representation, reward function, and learning algorithm. Machine learning methods have showed their advantages and potential in conflict detection and resolution related challenges. However, more studies would be conducted to improve their performances such as airspace network representation, multi-agent reinforcement learning or controller's strategy reconstruction from data
Amor, Yasmine. "Ιntelligent apprοach fοr trafic cοngestiοn predictiοn." Electronic Thesis or Diss., Normandie, 2024. http://www.theses.fr/2024NORMR129.
Full textTraffic congestion presents a critical challenge to urban areas, as the volume of vehicles continues to grow faster than the system’s overall capacity. This growth impacts economic activity, environmental sustainability, and overall quality of life. Although strategies for mitigating traffic congestion have seen improvements over the past few decades, many cities still struggle to manage it effectively. While various models have been developed to tackle this issue, existing approaches often fall short in providing real-time, localized predictions that can adapt to complex and dynamic traffic conditions. Most rely on fixed prediction horizons and lack the intelligent infrastructure needed for flexibility. This thesis addresses these gaps by proposing an intelligent, decentralized, infrastructure-based approach for traffic congestion estimation and prediction.We start by studying Traffic Estimation. We examine the possible congestion measures and data sources required for different contexts that may be studied. We establish a three-dimensional relationship between these axes. A rule-based system is developed to assist researchers and traffic operators in recommending the most appropriate congestion measures based on the specific context under study. We then proceed to Traffic Prediction, introducing our DECentralized COngestion esTimation and pRediction model using Intelligent Variable Message Signs (DECOTRIVMS). This infrastructure-based model employs intelligent Variable Message Signs (VMSs) to collect real-time traffic data and provide short-term congestion predictions with variable prediction horizons.We use Graph Attention Networks (GATs) due to their ability to capture complex relationships and handle graph-structured data. They are well-suited for modeling interactions between different road segments. In addition to GATs, we employ online learning methods, specifically, Stochastic Gradient Descent (SGD) and ADAptive GRAdient Descent (ADAGRAD). While these methods have been successfully used in various other domains, their application in traffic congestion prediction remains under-explored. In our thesis, we aim to bridge that gap by exploring their effectiveness within the context of real-time traffic congestion forecasting.Finally, we validate our model’s effectiveness through two case studies conducted in Muscat, Oman, and Rouen, France. A comprehensive comparative analysis is performed, evaluating various prediction techniques, including GATs, Graph Convolutional Networks (GCNs), SGD and ADAGRAD. The achieved results underscore the potential of DECOTRIVMS, demonstrating its potential for accurate and effective traffic congestion prediction across diverse urban contexts
Sainct, Rémi. "Étude des instabilités dans les modèles de trafic." Thesis, Paris Est, 2016. http://www.theses.fr/2016PESC1067/document.
Full textHighway traffic is known to be unstable when the vehicle density becomes too high, and to create stop-and-go waves, with an alternance of free flow and congested traffic. First-order traffic models can't reproduce these oscillations, but higher-order models can, both microscopic (car-following models) and macroscopic (systems of conservation laws).This thesis analyses the representation of unstable traffic states and oscillations in various traffic models. At the microscopic level, because of the flux concavity, the average flow of these oscillations is lower than the equilibrium flow for the same density. An algorithm is given to stabilize the flow with multi-anticipation, using an intelligent autonomous vehicle.At the macroscopic level, this work introduces averaged models, using the fact that the spatio-temporal scale of the oscillations is too small to be correctly predicted by simulations. The averaged LWR model, which consists of two conservation laws, enables a macroscopic representation of the density variance in a heterogeneous traffic, and gives the correct average flow of these states. A comparison with the ARZ model, also of order 2, shows that the averaged model can reproduce a capacity drop in a more realistic way.Finally, this thesis presents the SimulaClaire project of real-time traffic prediction on the ring road of Toulouse, and its parallelized parameter optimization algorithm
Leon, Ojeda Luis. "Short-term multi-step ahead traffic forecasting." Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENT081/document.
Full textThis dissertation falls within the domain of the Intelligent Transportation Systems (ITS). In particular, it is concerned with the design of a methodology for the real-time multi-step ahead travel time forecasting using flow and speed measurements from a instrumented freeway. To achieve this objective this thesis develops two main methodologies. The first one, a model-free, uses only speed measurements collected from the freeway, where a mean speed is assumed between two consecutive collection points. The travel time is forecasted using a noise Adaptive Kalman Filter (AKF) approach. The process noise statistics are computed using an online unbiased estimator, while the observations and their noise statistics are computed using the clustered historical traffic data. Forecasting problems are reformulated as filtering ones through the use of pseudo-observations built from historical data. The second one, a model-based, uses mainly traffic flow measurements. Its main appealing is the use of a mathematical model in order to reconstruct the internal state (density) in small road portions, and consequently exploits the relation between density and speed to forecast the travel time. The methodology uses only boundary conditions as inputs to a switched Luenberger state observer, based on the ``Cell Transmission Model'' (CTM), to estimate the road initial states. The boundary conditions are then forecasted using the AKF developed above. Consequently, the CTM model is run using the initial conditions and the forecasted boundaries in order to obtain the future evolution of densities, speeds, and finally travel time. The added innovation in this approach is the space discretization achieved: indeed, portions of the road, called ``cells'', can be chosen as small as desired and thus allow obtaining a finer tracking of speed variations. In order to validate experimentally the developed methodologies, this thesis uses as study case the Grenoble South Ring. This freeway, enclosing the southern part of the city from A41 to A480, consists of two carriageways with two lanes. For this study only the direction east-west was considered. With a length of about 10.5 km, this direction has 10 on-ramps, 7 off-ramps, and is monitored through the Grenoble Traffic Lab (GTL) that is able to provide reliable traffic data every 15 s, which makes it possible for the forecasting strategies to be validated in real-time. The results show that both methods present strong capabilities for travel time forecasting: considering the entire freeway, in 90% of the cases it was obtained a maximum forecasting error of 25% up to a forecasting horizon of 45 min. Furthermore, both methods perform as good as, or better than, the average historical. In particular, it is obtained that for horizons larger than 45 min, the forecasting depended exclusively on the historical data. For the dataset considered, the assessment study also showed that the model-based approach was more suitable for horizons shorter than 30 min
Zuo, Jingwei. "Apprentissage de représentations et prédiction pour des séries-temporelles inter-dépendantes." Electronic Thesis or Diss., université Paris-Saclay, 2022. http://www.theses.fr/2022UPASG038.
Full textTime series is a common data type that has been applied to enormous real-life applications, such as financial analysis, medical diagnosis, environmental monitoring, astronomical discovery, etc. Due to its complex structure, time series raises several challenges in their data processing and mining. The representation of time series plays a key role in data mining tasks and machine learning algorithms for time series. Yet, a few methods consider the interrelation that may exist between different time series when building the representation. Moreover, the time series mining requires considering not only the time series' characteristics in terms of data complexity but also the concrete application scenarios where the data mining task is performed to build task-specific representations.In this thesis, we will study different time series representation approaches that can be used in various time series mining tasks, while capturing the relationships among them. We focus specifically on modeling the interrelations between different time series when building the representations, which can be the temporal relationship within each data source or the inter-variable relationship between various data sources. Accordingly, we study the time series collected from various application contexts under different forms. First, considering the temporal relationship between the observations, we learn the time series in a dynamic streaming context, i.e., time series stream, for which the time series data is continuously generated from the data source. Second, for the inter-variable relationship, we study the multivariate time series (MTS) with data collected from multiple data sources. Finally, we study the MTS in the Smart City context, when each data source is given a spatial position. The MTS then becomes a geo-located time series (GTS), for which the inter-variable relationship requires more modeling efforts with the external spatial information. Therefore, for each type of time series data collected from distinct contexts, the interrelations between the time series observations are emphasized differently, on the temporal or (and) variable axis.Apart from the data complexity from the interrelations, we study various machine learning tasks on time series in order to validate the learned representations. The high-level learning tasks studied in this thesis consist of time series classification, semi-supervised time series learning, and time series forecasting. We show how the learned representations connect with different time series learning tasks under distinct application contexts. More importantly, we conduct the interdisciplinary study on time series by leveraging real-life challenges in machine learning tasks, which allows for improving the learning model's performance and applying more complex time series scenarios.Concretely, for these time series learning tasks, our main research contributions are the following: (i) we propose a dynamic time series representation learning model in the streaming context, which considers both the characteristics of time series and the challenges in data streams. We claim and demonstrate that the Shapelet, a shape-based time series feature, is the best representation in such a dynamic context; (ii) we propose a semi-supervised model for representation learning in multivariate time series (MTS). The inter-variable relationship over multiple data sources is modeled in a real-life context, where the data annotations are limited; (iii) we design a geo-located time series (GTS) representation learning model for Smart City applications. We study specifically the traffic forecasting task, with a focus on the missing-value treatment within the forecasting algorithm
Goncalves, Gomes Danielo. "Un modèle connexionniste pour la prédiction et l'optimisation de la bande passante : Approche basée sur la nature autosimilaire du trafic vidéo." Evry-Val d'Essonne, 2004. http://www.theses.fr/2004EVRY0021.
Full textThe objective of this thesis is the bandwidth forecasting optimization of a MPEG-4 video flow aggregate in a scenario of provisioning of Video on Demand (VoD) service over Internet. The proposed approach takes into account the self-similar nature of the IP traffic to estimate the Hurst parameter. This metric characterizes the degree of self-similarity of a process such as Internet traffic. A first contribution of this thesis is the design and implementation of a connectionist model which estimates and predicts the Husrt parameter of an aggregate video traffic. A new model called Predictive Connectionist Model (PCM) has been defined and is trained with MPEG traces patterns. The estimation of the bandwidth utilisation is achieved using two prediction techniques which evaluated and compared. Another contribution of this thesis is the integration of the Predictive Connectionist Model in a dynamic provisioning system between a VoD provider and an ISP (Internet Service Provider). This system is designed according to the Policy Based Management architecture of IETF (Internet Engineering Task Force) and is implemented using Web technologies
Ngo, Ha Nhi. "Apprentissage continu et prédiction coopérative basés sur les systèmes de multi-agents adaptatifs appliqués à la prévision de la dynamique du trafic." Electronic Thesis or Diss., Université de Toulouse (2023-....), 2024. http://www.theses.fr/2024TLSES043.
Full textLe développement rapide des technologies matérielles, logicielles et de communication des systèmes de transport ont apporté des opportunités prometteuses et aussi des défis importants pour la société humaine. Parallèlement à l'amélioration de la qualité des transports, l'augmentation du nombre de véhicules a entraîné de fréquents embouteillages, en particulier dans les grandes villes aux heures de pointe. Les embouteillages ont de nombreuses conséquences sur le coût économique, l'environnement, la santé mentale des conducteurs et la sécurité routière. Il est donc important de prévoir la dynamique du trafic et d'anticiper l'apparition des embouteillages, afin de prévenir et d'atténuer les situations de trafic perturbées, ainsi que les collisions dangereuses à la fin de la queue d'un embouteillage. De nos jours, les technologies innovatives des systèmes de transport intelligents ont apporté des ensembles de données diverses et à grande échelle sur le trafic qui sont continuellement collectées et transférées entre les dispositifs sous forme de flux de données en temps réel. Par conséquent, de nombreux services de systèmes de transport intelligents ont été développés basé sur l'analyse de données massives, y compris la prévision du trafic. Cependant, le trafic contient de nombreux facteurs variés et imprévisibles qui rendent la modélisation, l'analyse et l'apprentissage de l'évolution historique du trafic difficiles. Le système que nous proposons vise donc à remplir les cinq composantes suivantes d'un système de prévision du trafic : textbf{analyse temporelle, analyse spatiale, interprétabilité, analyse de flux et adaptabilité à plusieurs échelles de données} pour capturer les patterns historiques de trafic à partir des flux de données, fournir une explication explicite de la causalité entrée-sortie et permettre différentes applications avec divers scénarios. Pour atteindre les objectifs mentionnés, nous proposons un modèle d'agent basé sur le clustering dynamique et la théorie des systèmes multi-agents adaptatifs afin de fournir des mécanismes d'apprentissage continu et de prédiction coopérative. Le modèle d'agent proposé comprend deux processus interdépendants fonctionnant en parallèle : textbf{apprentissage local continu} et textbf{prédiction coopérative}. Le processus d'apprentissage vise à détecter, au niveau de l'agent, différents états représentatifs à partir des flux de données reçus. Basé sur le clustering dynamique, ce processus permet la mise à jour continue de la base de données d'apprentissage en s'adaptant aux nouvelles données. Simultanément, le processus de prédiction exploite la base de données apprise, dans le but d'estimer les futurs états potentiels pouvant être observés. Ce processus prend en compte l'analyse de la dépendance spatiale en intégrant la coopération entre les agents et leur voisinage. Les interactions entre les agents sont conçues sur la base de la théorie AMAS avec un ensemble de mécanismes d'auto-adaptation comprenant textbf{l'auto-organisation}, textbf{l'autocorrection} et textbf{l'auto-évolution}, permettant au système d'éviter les perturbations, de gérer la qualité de la prédiction et de prendre en compte les nouvelles informations apprises dans le calcul de la prédiction. Les expériences menées dans le contexte de la prévision de la dynamique du trafic évaluent le système sur des ensembles de données générées et réelles à différentes échelles et dans différents scénarios. Les résultats obtenus ont montré la meilleure performance de notre proposition par rapport aux méthodes existantes lorsque les données de trafic expriment de fortes variations. En outre, les mêmes conclusions retirées de différents cas d'étude renforcent la capacité du système à s'adapter à des applications multi-échelles
Hofleitner, Aude. "Développement d'un modèle d'estimation des variables de trafic urbain basé sur l'utilisation des technologies de géolocalisation." Phd thesis, Université Paris-Est, 2012. http://tel.archives-ouvertes.fr/tel-00798239.
Full textSchettini, Frédéric. "Fusion de données pour la surveillance du trafic et l'information des usagers." Toulouse, ENSAE, 1998. http://www.theses.fr/1998ESAE0016.
Full textLadino, lopez Andrés. "Traffic state estimation and prediction in freeways and urban networks." Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAT016/document.
Full textCentralization of work, population and economic growth alongside continued urbanization are the main causes of congestion. As cities strive to update or expand aging infrastructure, the application of big data, new models and analytics to better understand and help to combat traffic congestion is crucial to the health and development of our smart cities of XXI century. Traffic support tools specifically designed to detect, forecast and alert these conditions are highly requested nowadays.This dissertation is dedicated to study techniques that may help to estimate and forecast conditions about a traffic network. First, we consider the problem Dynamic Travel Time (DTT) short-term forecast based on data driven methods. We propose two fusion techniques to compute short-term forecasts from clustered time series. The first technique considers the error covariance matrix and uses its information to fuse individual forecasts based on best linear unbiased estimation principles. The second technique exploits similarity measurements between the signal to be predicted and clusters detected in historical data and it performs afusion as a weighted average of individual forecasts. Tests over real data were implemented in the study case of the Grenoble South Ring, it comprises a highway of 10.5Km monitored through the Grenoble Traffic Lab (GTL) a real time application was implemented and open to the public.Based on the previous study we consider then the problem of simultaneous density/flow reconstruction in urban networks based on heterogeneous sources of information. The traffic network is modeled within the framework of macroscopic traffic models, where we adopt Lighthill-Whitham-Richards (LWR) conservation equation and a piecewise linear fundamental diagram. The estimation problem considers two key principles. First, the error minimization between the measured and reconstructed flows and densities, and second the equilibrium state of the network which establishes flow propagation within the network. Both principles are integrated together with the traffic model constraints established by the supply/demand paradigm. Finally the problem is casted as a constrained quadratic optimization with equality constraints in order to shrink the feasible region of estimated variables. Some simulation scenarios based on synthetic data for a manhattan grid network are provided in order to validate the performance of the proposed algorithm
Uzunova, Milka. "Commande non-entière des systèmes. : développement et application pour les modèles du flux de trafic routier." Thesis, Artois, 2009. http://www.theses.fr/2009ARTO0205/document.
Full textThis thesis presents research carried out to several elements of the macroscopic traffic flow as the model, the control and the simulation of his control system. The main aims of the realized studies consist to keep the circulation on the high-ways fluid. That means that we must to assure some quality of the process regarding the stability of this process. More over to offer best performances and quality of the traffic services for the users on the ways networks.In our study we use the analytical solution method of the dynamic equation presenting the LWR traffic flow model process, for which we look to obtain transfer function. Our objective is to obtain a conform result to a toll plaza. Furthermore we look to make a choice of appropriate control algorithm to satisfy the traffic network and users’ needs. The traffic flow management needs results from the increasingly of the flows. As consequence of this we can obtain saturation in some places in the road network wildly known as a traffic jam usually in the rush hours, by reason of accident or repairs works. All this provoke a delay of the transportation flow and important environmental after-effect. Therefore it’s very important to assure the fluidity of the traffic using control strategies which will cancel, reduce or delay the traffic jam appearances. Because of all the reasons above, we have proposed a system with non-integer order control algorithm for maintain the traffic fluid by the control of the pikes in the toll plaza. The control variable is the upstream density which will influence on the downstream one. After the analytical solution of the toll plaza model we obtain a delay function which presents the plant in our distributed parameter system. For this system we apply a Smith prediction non-integer control algorithm and moreover we ameliorate this system with a Dead time non-integer order compensator
Bermolen, Paola. "Modèles probabilistes et statistiques pour la conception et l'analyse des systèmes de communications." Phd thesis, Télécom ParisTech, 2010. http://pastel.archives-ouvertes.fr/pastel-00005853.
Full textMarceau, Caron Gaetan. "Optimization and uncertainty handling in air traffic management." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112183/document.
Full textIn this thesis, we investigate the issue of optimizing the aircraft operators' demand with the airspace capacity by taking into account uncertainty in air traffic management. In the first part of the work, we identify the main causes of uncertainty of the trajectory prediction (TP), the core component underlying automation in ATM systems. We study the problem of online parameter-tuning of the TP during the climbing phase with the optimization algorithm CMA-ES. The main conclusion, corroborated by other works in the literature, is that ground TP is not sufficiently accurate nowadays to support fully automated safety-critical applications. Hence, with the current data sharing limitations, any centralized optimization system in Air Traffic Control should consider the human-in-the-loop factor, as well as other uncertainties. Consequently, in the second part of the thesis, we develop models and algorithms from a network global perspective and we describe a generic uncertainty model that captures flight trajectories uncertainties and infer their impact on the occupancy count of the Air Traffic Control sectors. This usual indicator quantifies coarsely the complexity managed by air traffic controllers in terms of number of flights. In the third part of the thesis, we formulate a variant of the Air Traffic Flow and Capacity Management problem in the tactical phase for bridging the gap between the network manager and air traffic controllers. The optimization problem consists in minimizing jointly the cost of delays and the cost of congestion while meeting sequencing constraints. In order to cope with the high dimensionality of the problem, evolutionary multi-objective optimization algorithms are used with an indirect representation and some greedy schedulers to optimize flight plans. An additional uncertainty model is added on top of the network model, allowing us to study the performances and the robustness of the proposed optimization algorithm when facing noisy context. We validate our approach on real-world and artificially densified instances obtained from the Central Flow Management Unit in Europe
Smaili, Samia. "Modélisation et commande d'un système de trafic multimodal." Phd thesis, Université d'Evry-Val d'Essonne, 2012. http://tel.archives-ouvertes.fr/tel-00684018.
Full textKachroudi, Sofiene. "Commande et optimisation pour la régulation du trafic urbain mutimodale sur de grands réseaux urbains." Thesis, Evry-Val d'Essonne, 2010. http://www.theses.fr/2009EVRY0035/document.
Full textThe need for traffic regulation and improving the transit regularity are facts widely shared within the research and operational environments. The objective of this thesis is to design a strategy to meet these goals through the traffic lights on large urban networks. Topics addressed in this thesis are: traffic modelling: whether it is for general or transit vehicles. For the former, the model reproduces the basic patterns already developed with improvements to accommodate all traffic situations. For transit vehicles, two original models were developed. Construction of criteria: we have constructed two criteria to measure the traffic state. The first, for cars, is the same as that used in other systems of traffic control. The criterion for transit vehicles has been built in an original way to measure the regularity of the vehicles. Multi-objective optimization: the models complexity, the highly non-linear criteria and the constraints of real-time environment have guided the choice of a meta-heuristic called Particle Swarm Optimization. We have implemented two versions and adapted the scheme to the multi-objective case. Closed loop control: the strategy had to respond in real time to changing trafic conditions. We have adopted a classic architecture of the Generalized Model Predictive control and an architecture involving predictive control and the linear quadratic control. This last one is used to initialize and limit the size of the search space for the optimization algorithm. The numerical results obtained by simulation on a virtual network show that the strategy significantly improves the overall traffic and regularity of the transit lines
Majid, Hirsh. "Contribution à l'estimation et à la commande des systèmes de transport intelligents." Thesis, Artois, 2014. http://www.theses.fr/2014ARTO0203/document.
Full textThe works presented in this PhD dissertation fit into the framework of Intelligent TransportationSystems. Although the beginnings of these systems have started since the 60s, their development, basedon information and communication technologies, has reached maturity during the early 80s. The ITS usesthe intelligence of different systems (embedded systems, intelligents sensors, intelligents highways, etc.)in order to optimize road infrastructures performances and respond to the daily problems of congestions.The dissertation presents four contributions into the framework of road traffic flow and tackles theestimation and control problems in order to eliminate or at least reduce the “recurrent" congestionsphenomena. The first point treats the problem of traffic state estimation which is of most importance inthe field of ITS. Indeed, the implementation and performance of any control strategy is closely relatedto the ability to have all needed information about the traffic state describing the dynamic behavior ofthe studied system. Two estimation algorithms are then proposed. The first one uses the “metanet"model and high order sliding mode techniques. The second is based on the so-called Cell TransmissionModels. Several comparative studies with the Kalman filters, which are the most used in road traffic flowengineering, are established in order to demonstrate the effectiveness of the proposed approaches. Thethree other contributions concern the problem of traffic flow control. At first, the focus is on the isolatedramp metering using an algorithm based on the high order sliding mode control. The second contributiondeals with the dynamic traffic routing problem based on the high order sliding mode control. Such controlstrategy is enriched by introducing the concept of integration, in the third contribution. Indeed, integratedcontrol consists of a combination of several traffic control algorithms. In this thesis the proposed approachcombines an algorithm of on-ramp control with a dynamic traffic routing control. The obtained results arevalidated via numerical simulations. The validated results of the proposed isolated ramp metering controlare compared with the most used ramp metering strategy : ALINEA. Finally, the last contributiontreats the coordination problems. The objective is to coordinate several ramps which cooperate andchange information in order to optimize the highway traffic flow and reduce the total travel time in theapplied area. All these contributions were validated using real data mostly from French freeways. Theobtained results show substantial gains in term of performances such as travel time, energetic consumptiondecreasing, as well as the increasing in the mean speed. These results allow to consider several furtherworks in order to provide more interesting and efficient solutions in the ITS field
Ivagnes, Alexandre. "Valeur prédictive du récepteur NKp30 dans la réponse à l’imatinib mesylate des tumeurs stromales gastrointestinales et identification d’un nouveau mécanisme inhibiteur des cellules Natural Killer par la voie TNFα/TNFR2/BIRC3/TRAF1." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS237/document.
Full textOver the last 10 years, immunotherapy has been at the forefront of cancer therapy. Natural Killer (NK) cells are part of the innate immune system and have the unique ability to lyse tumor cells without any antigen specific priming. They have a key prognostic role in several hematological and solid cancers including gastrointestinal stromal tumors (GIST). A balance between activating and inhibitory receptors triggers NK cell activation. Natural cytotoxicity receptors (NCR) are among the most clinically relevant activating receptors and include NKp30, NKp44 and NKp46. NKp30 can be expressed in 3 different isoforms: NKp30a and NKp30b are both immunostimulatory, inducing interferon (IFN) γ and tumor necrosis factor (TNF) α secretion whereas NKp30c is immunosuppressive, producing interleukin 10 (IL-10). IFNγ is a potent activator of immune cells whereas IL-10 is an anti-inflammatory cytokine. TNFα was first described as a serum factor, inducing tumor necrosis but its role has since been broadened to homeostatic functions. Ample evidence suggests that anti-tumor functions of NK cells are tightly regulated and expand far beyond the simple killing of malignant cells. Despite the tremendous progress in understanding NK cell biology, further work is warranted to fully exploit the anticancer potential of these cells.Our group demonstrated the crucial role that NK cells have in GIST. Indeed, NK cell infiltrate positively correlates with progression-free survival. Moreover, we showed that the preferential expression of the immunosuppressive isoform NKp30c, negatively impacts the clinical outcome of GIST patients. To further extend these observations, we explored the influence of various NKp30 isoforms in GIST patients.Firstly, we revealed that a high ratio between the expression of NKp30b and NKp30c isoforms predicted a stronger imatinib mesylate (IM) response (a tyrosine kinase inhibitor, TKI – first line standard of care in GIST) and that tumor cytokine milieu is modified following NKp30 isoform expression. Furthermore, we demonstrated a link between the presence of soluble ligands of NKp30, soluble B7 Homolog 6 (sB7-H6) and soluble BCL2 Associated Athanogene 6 (sBAG6), and a decrease in event-free survival in IM-treated GIST patients.Despite the presence of immune infiltration in many tumors, antitumor functions of lymphocytes are inhibited by the tumor microenvironment. Thus, we explored which signaling pathways were associated with NK cell inhibition in the tumor microenvironment. To do so, we performed a microarray from GIST infiltrating NK cells which highlighted the deleterious effect of TNFα/TNF Receptor 2/Baculoviral IAP Repeat Containing 3 (BIRC3)/TNF Receptor Associated Factor 1 (TRAF1) pathway on the function of NK cells. Next, we demonstrated that activation of this pathway in NK cells decreased gene transcription and protein expression of the activating receptor NKp46 (also called Natural Cytotoxicity Triggering Receptor 1 NCR1). This decrease positively correlated with NKp30c isoform expression. Moreover we showed that in mice, TNFα increases the metastatic dissemination of the NK sensitive tumor cell line, B16F10.Results from our research on NK cells strengthen the potential of NK cells as a therapeutic target for anti-tumor immunotherapy. Taken together, this thesis demonstrates the key role of the NKp30 receptor and its isoforms in the IM therapy as predictive marker in GIST response and describes for the first time a new NK cell inhibitory mechanism via the TNFα/TNFR2/BIRC3/TRAF1 pathway, paving the way for novel therapeutic strategies in cancer treatment
Chtioui, Maher. "L'exploitation de l'auto-similarité pour la prédiction du trafic Internet." Mémoire, 2006. http://www.archipel.uqam.ca/2117/1/M9165.pdf.
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