Hypoxia Promotes Tumor Growth in Linking Angiogenesis to Immune Escape

Despite the impressive progress over the past decade, in the field of tumor immunology, such as the identification of tumor antigens and antigenic peptides, there are still many obstacles in eliciting an effective immune response to eradicate cancer. It has become increasingly clear that tumor microenvironment plays a crucial role in the control of immune protection. Tumors have evolved to utilize hypoxic stress to their own advantage by activating key biochemical and cellular pathways that are important in progression, survival, and metastasis. Hypoxia-inducible factor (HIF-1) and vascular endothelial growth factor (VEGF) play a determinant role in promoting tumor cell growth and survival. Hypoxia contributes to immune suppression by activating HIF-1 and VEGF pathways. Accumulating evidence suggests a link between hypoxia and tumor tolerance to immune surveillance through the recruitment of regulatory cells (regulatory T cells and myeloid derived suppressor cells). In this regard, hypoxia (HIF-1α and VEGF) is emerging as an attractive target for cancer therapy. How the microenvironmental hypoxia poses both obstacles and opportunities for new therapeutic immune interventions will be discussed

Etude de la réponse cytotoxique lors de la progression tumorale (rôle de la cytokeratine 18)

PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

L’hypoxie tumorale

L’hypoxie est une caractéristique majeure de la plupart des tumeurs solides. Les cellules s’adaptent à la baisse de l’apport en oxygène en stabilisant les facteurs de transcription HIF (hypoxia-inducible factor) qui, à leur tour, activent l’expression de nombreux gènes résultant en la survie et le maintien des fonctions cellulaires. Dans les cellules tumorales, l’exposition au stress hypoxique active, via les facteurs HIF, une série de molécules qui leur permettent de résister à la lyse dépendante des cellules tueuses du système immunitaire. L’hypoxie tissulaire régule également les fonctions des cellules de l’immunité et leur différenciation. Cette revue décrit les mécanismes de résistance tumorale aux effecteurs cytotoxiques induits par l’hypoxie, et les conséquences fonctionnelles de l’hypoxie sur les cellules immunes

Hypoxia: a key player in antitumor immune response. A Review in the Theme: Cellular Responses to Hypoxia

International audienceThe tumor microenvironment is a complex system, playing an important role in tumor development and progression. Besides cellular stromal components, extracellular matrix fibers, cytokines, and other metabolic mediators are also involved. In this review we outline the potential role of hypoxia, a major feature of most solid tumors, within the tumor microenvironment and how it contributes to immune resistance and immune suppression/tolerance and can be detrimental to antitumor effector cell functions. We also outline how hypoxic stress influences immunosuppressive pathways involving macrophages, myeloid-derived suppressor cells, T regulatory cells, and immune checkpoints and how it may confer tumor resistance. Finally, we discuss how microenvironmental hypoxia poses both obstacles and opportunities for new therapeutic immune interventions

Design framework for the development of tailored behavior change technologies

International audienc

Démarche de conception participative d’une application mobile motivationnelle pour l’autogestion de la lombalgie chronique

IHM'23 - 34e Conférence Internationale Francophone sur l'Interaction Humain-MachineAFIHM, Université de Technologie de TroyesThe market for mobile health applications is growing rapidly, but few of these applications are based on evidence-based guidelines. In the case of chronic low back pain, some studies have attempted to identify user needs in order to propose recommendations for the design of digital interventions. However, the specification of human-machine interactions adapted to these needs is poorly described. In this study, we propose a participatory design approach for the design of a mobile application to support self-management of low back pain. We present the results of qualitative and quantitative methods to identify patients' needs and specify the associated human-machine interactions. Then we present the results of workshops conducted with patients in order to validate the human-machine interactions adapted to the previously identified needs. Finally, we propose several recommendations for the design of a mobile application for self-management of chronic low back pain.Le marché des applications mobiles pour la santé est en pleine expansion, mais peu de ces applications reposent sur des directives fondées sur des preuves. Dans le cas de la lombalgie chronique, certaines études ont tenté d’identifier les besoins des utilisateurs afin de proposer des recommandations pour la conception d'interventions digitales. Cependant, la spécification des interactions humain-machine adaptées à ces besoins est peu décrite. Dans cette étude, nous proposons une démarche de conception participative pour la conception d’une application mobile d’aide à l’autogestion de la lombalgie. Nous présentons les résultats de méthodes qualitatives et quantitatives pour identifier les besoins des patients et spécifier les interactions humain-machine associées. Ensuite nous présentons les résultats des ateliers menés avec des patients afin de valider les interactions humain-machine adaptées aux besoins identifiés précédemment. Enfin, nous proposons plusieurs recommandations pour la conception d’une application mobile d’autogestion de la lombalgie chronique

Profiling of low back pain patients for the design of a tailored coaching application

International audienc

In Vivo Prevention of Bladder Urotoxicity: Purified Hydroxytyrosol Ameliorates Urotoxic Effects of Cyclophosphamide and Buthionine Sulfoximine in Mice

International audienceUrotoxicity is a troublesome complication associated with cyclophosphamide (CP) and L-buthionine-SR-sulfoximine (BSO) treatment in chemotherapy. With this concern in mind, the present study investigated the potential effects of a hydroxytyrosol extract from olive mill waste (OMW) on urotoxicity induced by acute CP and BSO doses using a Swiss albino mouse model. Toxicity modulation was evaluated by measuring lipid peroxidation (LPO) and antioxidants in urinary bladder. The findings revealed that the hydroxytyrosol extract exerted a protective effect not only on LPO but also on enzymatic antioxidants. When compared to the controls, the CP-treated animals underwent significant decreases in the glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GP), and catalase (CAT) activities. The level of glutathione (GSH) was also reduced with increased doses of LPO in the CP-treated animals. L-Buthionine-SR-sulfoximine treatment exerted an additive toxic effect on the CP-treated animals. Interestingly, pretreatment with the hydroxytyrosol extract restored the activities of all enzymes back to normal levels and exhibited an overall protective effect on the CP- and BSO-induced toxicities in urinary bladder. The restoration of GSH through the treatment with the hydroxytyrosol extract can play an important role in reversing CP-induced apoptosis and free radical-mediated LPO