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Lung cancer is the most frequent cause of death in cancer patients in industrialized countries. Most patients with advanced nonsmall cell lung cancer (NSCLC) do not respond to the current treatment schemes indicating that the basic mechanisms of tumorigenesis and metastasis are insufficiently understood, hence impeding both diagnosis and targeted treatment. A particular property of NSCLC is the composition of the tumor microenvironment with a very high proportion of stromal cells. These nontransformed compartments of the tumor microenvironment are crucial cellular structures supporting tumor growth and could hence function as universal targets for tumor therapy. Although cancerassociated mesenchymal stromal cells, including NSCLC associated myofibroblasts, critically contribute to the establishment and maintenance of the tumor microenvironment, a thorough functional characterization of these important cells has been lacking. Novel systems biology approaches such as transcriptome analysis of human lung cancer cells on the gene and exon level have been established in the Division of Pneumology to molecularly classify NSCLCs and to predict the survival of NSCLC patients. Furthermore, new models of mesenchymal stromal cell targeting have been established in the Institute of Immunobiology which facilitate (i) genetic definition of mesenchymal stromal cell populations in different tumor entities, (ii) in vivo labelling and tracking of particular mesenchymal stromal cell populations, (iii) molecular characterization of highly purified subpopulations of mesenchymal stromal cells using transcriptomics and/or proteomics approaches, (iv) selective ablation of particular cellular subsets within the tumor stroma, and (v) functional assessment of molecularly defined target structures in mesenchymal stromal cell populations.