The microenvironment in lymphomas--dissecting the complex crosstalk between tumor cells and 'by-stander' cells.

In lymphomas, it is increasingly apparent that the microenvironment is an essential player not only for lymphoma pathogenesis but also for disease progression and therapy resistance. In recent years, we have begun to understand the complex crosstalk between the neoplastic cells and other immune cells, such as T and NK cells, and stromal cells, as well as the signaling pathways that become aberrantly activated through this dialogue (e.g. B-cell receptor, Toll-like receptor and NF-?B signaling). In this series of reviews, the intricate interplay between lymphoma cells and 'by-stander' cells will be illustrated in representative lymphoma entities, namely Hodgkin lymphomas, follicular lymphomas, marginal-zone lymphomas, chronic lymphocytic leukemia, and T-cell lymphomas, where the crucial role played by the microenvironment has become particularly evident. Furthermore, important clues to the pathobiology of lymphomas have emerged from (i) the recognition of pre-malignant conditions, such as monoclonal B-cell lymphocytosis or in situ lymphomas, (ii) the identification of microbial and/or auto-antigens that are linked to particular entities, as well as (iii) the established increased risk of lymphomas in certain autoimmune/inflammatory conditions, all critical aspects that will be further elaborated in this thematic issue. Our increasing knowledge of these interactions and associations has finally allowed us to design targeted or immune-mediated strategies to interfere with the lymphoma microenvironment, thereby opening promising therapeutic avenues on the road to cure for these yet incurable diseases.