70INTHE TUMOUR MICROENVIRONMENT AS A BARRIER FOR IMMUNE DESTRUCTION OF CANCER

Abstract Solid tumors are more than an accumulation of cancer cells. Indeed, cancerous cells create a immune permissive microenvironment by exploiting non-transformed host cells. Thus, solid tumors rather resemble abnormal organs composed of the tumor cells itself and the stroma providing the supportive framework. The stroma can be divided into the extracellular matrix consisting of proteoglycans, hyaluronic acid, and fibrous proteins, as well as stromal cells including mesenchymal and immune cells; moreover, it contains various peptide factors and metabolites. Each of these components may exert immune modulating effects. More recent advances have further revealed that tumor-host interactions extend well beyond the local microenvironment. Indeed, similar to organs tumors are not existing on their own, but take up residence in the host, i.e. the patient. Moreover, tumors not only respond to, but actively perturb host organs at distant anatomic sites in order to facilitate immune escape and metastatic spread, e.g. by modification of fibroblasts and the extracellular matrix at premetastatic sites. However, the detailed modus operandi of the crosstalk between tumor cells, the tumor microenvironment and the host macroenvironment to date is not completely understood. Emerging mechanisms of communication include miRNAs as well as tumor-derived exosomes. The latter contribute to metastatic invasion by carrying both messenger proteins (as well as mRNAs, miRNAs, and DNA) that direct bone marrow–derived cells toward a prometastatic phenotype or do generate a state of chronic inflammation. Consequently, many aspects of tumor biology and tumor immunology can only be explained by a detailed understanding of both local and systemic interactions. Disclosure: The author has declared no conflicts of interest.