Abstract

Abstract

The tumor microenvironment is composed of different cells that can be grouped into three classes: cancer-associated fibroblasts, vascular cells and infiltrating immune cells. The relative abundance of these respective cell types as well as their polarization profile can greatly vary and often predicts prognosis and response to therapy. Cells of all three groups can control tumor cell proliferation, cell death, growth suppressor evasion, energy metabolism, angiogenesis, immune evasion as well as invasion in a non-autonomous manner. Thus, it has become unequivocally evident that tumor development depends on the intricate reciprocal interplay of mutagenized tumor cells with their local and distant microenvironment. Cytokines and other signal proteins control the plasticity of stromal, tumor and cancer stem like cells in an autocrine and paracrine manner thereby shaping the complex cellular contexture, which ultimately forms a pro- or anti-tumorigenic milieu. A detailed understanding of the cellular and molecular mechanisms underlying these complex interactions of tumor, stroma and immune cells may help to identify novel therapeutic targets. We recently identified signaling pathways during early and late tumorigenesis that highlight the importance of tumor cells for T cell polarization and suppression of adaptive immunity and that help to understand why stroma-rich colon tumors may be associated with a worse prognosis.