ECM–immune crosstalk and tissue remodeling

Intro

This session explores how extracellular matrix remodeling and immune crosstalk drive tissue remodeling in fibrosis and cancer, with a focus on liver disease. Chronic inflammation reshapes ECM composition, which in turn regulates immune activation, fibrogenesis, and tumor progression. Together, the presentations highlight the ECM as an active regulator of immune function and a central driver of liver fibrosis, opening new avenues for biomarkers and targeted therapies.

Immune cell – ECM interaction in fibrosis and cancer

Detlef Schuppan, Professor and Director of the Institute of Translational Immunology and the Clinical Center for Celiac, Small Intestinal, Metabolic and Autoimmune Diseases, Mainz University Medical Center.

Abstract: Inflammation alters the composition of the ECM and the ECM regulates immune cell activation. This applies to organ fibrosis and to solid cancers, and finally determines organ architecture and function, and cancer cell growth. Classical, usually acute and subacute inflammation stimulates ECM turnover and degradation and promotes and anti-cancer immune response, whereas chronic low grade inflammation usually characterizes immune cell exhaustion and an immune suppressive and profibrogenic tissue response. Key involved immune cells in these processes are monocytes-macrophages, dendritic cells, CD8+ T cells, CD4+ regulatory T cells, B cells and less well defined regulatory B cells. These cells modulate not the phenotype, function, growth or survival of the other cells like (myo) fibroblasts, endothelial and epithelial cells, or other immune cells, but are also critically regulated by an expanding plethora of ECM molecules, their biologically active fragments and respective cellular receptors. These include collagens, such as types VI, XI, XIV and XVIII, periostin, osteopontin, tenascin, fibronectins, laminins, thrombospondins-1/2 isoforms, proteoglycans, such as versican, and ECM receptors like DDR1, LAIR, CD44, CD147 and various integrins.  Moreover, ECM molecules like certain collagens, matricellular proteins and proteoglycans specifically bind fibrogenic or epithelial (tumor promoting) growth factors like PDGF-B, TGFb1, OSM, KGF or HGF which become liberated and active during inflammatory tissue remodeling.  The specific role of immune cell interactions with the ECM and specific ECM fragments in hot vs cold fibrosis or stroma poor vs stroma-rich cancers are still incompletely understood, but hold promise for novel ECM- and ECM receptor targeted therapeutic approaches in fibrosis and cancer, particularly downregulation of these molecules via targeted nanoparticular delivery of small molecules, siRNA or antisense oligonucleotides which will affect abnormal ECM composition, immune cell function and also other (immune modulatory) effector cells like (myo) fibroblasts and endothelial cells in fibrosis and cancer.

Title TBD

Douglas Maya Miles, Professor in the Department of Physiology at the University of Seville

Abstract: TBD