Lymphomas and Their Microenvironment: A Multifaceted Relationship

It has become evident that the microenvironment - lymphocytes, macrophages, fibroblasts as well as the extracellular matrix, cytokines, chemokines, and a plethora of other cells, structures and substances residing in the vicinity of tumor cells - plays an important part in the maintenance of cancer growth and survival. This is also relevant in lymphomas. In this review, we give an outline on the importance of the microenvironment for tumors in general and lymphomas in particular, by highlighting certain basic principles of tumor-microenvironment interaction. The relationship of lymphomas and their microenvironment is multifaceted: lymphoma cells need growth factors and cytokines derived from microenvironmental cells for their sustenance and growth. On the contrary, many lymphomas silence or at least deregulate the immune system to escape recognition and subsequent elimination by immune cells, while giving advantage to suppressive microenvironmental compounds such as M2 polarized macrophages, regulatory T-cells, mast cells, and immunosuppressive fibroblasts. We also give a detailed insight across different lymphoma types to show the variety of tumor-microenvironment interactions. Due to its tremendous importance, the microenvironment has also become a new target for oncologic therapy. The most important finding concerning lymphomas with a focus on immunomodulatory substances is also, therefore, highlighted.