Microenvironment signaling driving lymphomagenesis.

PURPOSE OF REVIEW: In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment. RECENT FINDINGS: Lymphoma supportive niche integrates a dynamic and orchestrated network of immune and stromal cell subsets producing, with a high level of spatial and kinetic heterogeneity, extracellular and membrane factors regulating tumor migration, survival, proliferation, immune escape, as well as tumor microarchitecture, and mechanical constraints. Some recent insights have improved our understanding of these various components of lymphoma microenvironment, taking into account the mechanisms underlying the coevolution of malignant and nonmalignant cells within the tumor niche. SUMMARY: Deciphering tumor niche characteristics, functions, and origin could offer new therapeutic opportunities through the targeting of pivotal cellular and molecular components of the supportive microenvironment, favoring immune cell reactivation and infiltration, and/or limiting tumor retention within this protective niche.