[The ambiguous role of the inflammatory micromilieu in solid tumors].

BACKGROUND: Besides host defense against infections, the main function of the immune system is to eliminate tumor cells. Therefore, nearly, all solid tumors have a heterogeneous fibro-inflammatory microenvironment, which consists of myofibroblastic cells, extracellular matrix components, and infiltrates from various types of immune cell. In particular, pancreatic ductal adenocarcinoma is a prototype of a tumor with a pronounced inflammatory microenvironment, in which the majority of the tumor mass consists of nonneoplastic stromal and immune cells. Our own data and data from the literature indicate a protective role of tumor-infiltrating T cells for the host. On the other hand, we were able to show that a defined T cell subpopulation paradoxically promotes the progression of the tumor. Our investigations now focus on these cells, known as "Th17," in the tumor microenvironment.
OBJECTIVES: To elucidate the mechanisms of the infiltrated immune cells and their mediators in the tumor microenvironment.
MATERIALS AND METHODS: Human pancreatic cancer tissue was used for (immune) histological staining and morphometric analysis and the results were correlated with clinical parameters and with diffusion-weighted magnetic resonance imaging images. The molecular mechanisms were analyzed in cell culture approaches using human tumor cells and human immune cells. With molecular biological methods and functional assays cell growth, invasion and colony formation were assessed. The in vivo correlation of the results and functional interventions were tested in murine and avian (xenograft) models. RESULTS AND
CONCLUSION: Tumor-infiltrating immune cells of type Th17 and their mediators promoted the progression of the tumor depending on density, activation status, and cytokine profile. On molecular level, we identified a Th17-mediated increase of tumor cell migration and invasion, an increased neoangiogenesis, as well as a reorganization of the tumor stroma and microarchitecture. The data show that the progression of pancreatic cancer, depends on the status of activation and the cytokine profile of the infiltrated T cells.