The stroma is a considerable part of the tumor microenvironment. Because of its complexity, it can influence both cancer and immune cells in their behavior and cross-talk. Aside from soluble products released by non-cancer and cancer cells, extracellular matrix components have been increasingly recognized as more than just minor players in the constitution, development and regulation of the tumor microenvironment. The variations in the connective scaffold architecture, induced by transforming growth factor beta, lysyl oxidase and metalloproteinase activity, create different conditions of ECM density and stiffness. They exert broad effects on immune cells (e.g. physical barriers, modulation by release of stored TGF-β1), mesenchymal cells (transition to myofibroblasts), epithelial cells (epithelial-to-mesenchymal transition), cancer cells (progression to metastatic phenotype) and stem cells (activation of differentiation addressed by the microenvironment characteristics). Physiological mechanisms of the wound healing process, as well as mechanisms of fibrosis in some chronic pathologies, closely recall aspects of cancer deregulated biology. Their elucidation can provide a better understanding of tumor microenvironment immunobiology. In the following short review, we will focus on some aspects of the fibrous stroma to highlight its active participation in the tumor microenvironment constitution, tumor progression and the local immunological network.

Laboratory of Immunotherapy Institute of Microbiology Academy of Sciences of the Czech Republic v v i Videnska 1083 142 20 Prague 4 Czech Republic

Laboratory of Tumor Biology Institute of Animal Physiology and Genetics Academy of Sciences of the Czech Republic v v i Rumburska 89 277 21 Libechov Czech Republic

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Local Immune Changes in Early Stages of Inflammation and Carcinogenesis Correlate with the Collagen Scaffold Changes of the Colon Mucosa

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Lysyl oxidases: linking structures and immunity in the tumor microenvironment