by Keyword: Interleukin-2
Perucca, Alice, Llonin, Andrea Gomez, Benach, Oriol Mane, Hallopeau, Clement, Rivas, Elisa I, Rivas, Elisa I, Linares, Jenniffer, Garrido, Marta, Sallent-Aragay, Anna, Golde, Tom, Colombelli, Julien, Dalaka, Eleni, Linacero, Judith, Cazorla, Marina, Galan, Teresa, Pastor Viel, Jordi, Badenas, Xavier, Recort-Bascuas, Alba, Comerma, Laura, Fernandez-Nogueira, Patricia, Rovira, Ana, Roca-Cusachs, Pere, Albanell, Joan, Trepat, Xavier, Calon, Alexandre, Labernadie, Anna, (2025). Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing Nature Communications 16, 1279 
Immunotherapies are beneficial for a considerable proportion of cancer patients, but ineffective in others. In vitro modelling of the complex interactions between cancer cells and their microenvironment could provide a path to understanding immune therapy sensitivity and resistance. Here we develop MIRO, a fully humanised in vitro platform to model the spatial organisation of the tumour/stroma interface and its interaction with immune cells. We find that stromal barriers are associated with immune exclusion and protect cancer cells from antibody-dependent cellular cytotoxicity, elicited by targeted therapy. We demonstrate that IL2-driven immunomodulation increases immune cell velocity and spreading to overcome stromal immunosuppression and restores anti-cancer response in refractory tumours. Collectively, our study underscores the translational value of MIRO as a powerful tool for exploring how the spatial organisation of the tumour microenvironment shapes the immune landscape and influences the responses to immunomodulating therapies.
JTD Keywords: Activation, Animals, Architecture, Breast-cancer, Cancer-associated fibroblasts, Cell line, tumor, Collagen, Female, Humans, Immunomodulation, Immunotherapy, Interleukin-2, Lab-on-a-chip devices, Mechanism, Mice, Microenvironment, Migration, Neoplasms, Stromal cells, T-cells, Therap, Tumor microenvironment
Schierwagen, R, Gu, WY, Brieger, A, Brüne, B, Ciesek, S, Dikic, I, Dimmeler, S, Geisslinger, G, Greten, FR, Hermann, E, Hildt, E, Kempf, VAJ, Klein, S, Koch, I, Mühl, H, Müller, V, Peiffer, KH, Kestner, RI, Piiper, A, Rohde, G, Scholich, K, Schulz, MH, Storf, H, Toptan, T, Vasa-Nicotera, M, Vehreschild, MJGT, Weigert, A, Wild, PJ, Zeuzem, S, Engelmann, C, Schaefer, L, Welsch, C, Trebicka, J, (2023). Pathogenetic mechanisms and therapeutic approaches of acute-to-chronic liver failure American Journal Of Physiology-Cell Physiology 325, C129-C140
Liver cirrhosis is the end stage of all chronic liver diseases and contributes significantly to overall mortality of 2% globally. The age-standardized mortality from liver cirrhosis in Europe is between 10 and 20% and can be explained by not only the development of liver cancer but also the acute deterioration in the patient's overall condition. The development of complications including accumulation of fluid in the abdomen (ascites), bleeding in the gastrointestinal tract (variceal bleeding), bacterial infections, or a decrease in brain function (hepatic encephalopathy) define an acute decompensation that requires therapy and often leads to acute-on-chronic liver failure (ACLF) by different precipitating events. However, due to its complexity and organ-spanning nature, the pathogenesis of ACLF is poorly understood, and the common underlying mechanisms leading to the development of organ dysfunction or failure in ACLF are still elusive. Apart from general intensive care interventions, there are no specific therapy options for ACLF. Liver transplantation is often not possible in these patients due to contraindications and a lack of prioritization. In this review, we describe the framework of the ACLF-I project consortium funded by the Hessian Ministry of Higher Education, Research and the Arts (HMWK) based on existing findings and will provide answers to these open questions.
JTD Keywords: 12/15-lipoxygenase, combination, inflammation, interleukin-22, metabolism, mortality, organ failure, portal-hypertension, receptor, regeneration, systemic inflammation, systems medicine, translational hepatology, Decompensated cirrhosis, Organ failure, Systemic inflammation, Systems medicine, Translational hepatology
