Role of the microenvironment across histological subtypes of NHL

Recent progress in next-generation sequencing strategies has revealed the genetic landscape of B-cell non-Hodgkin lymphoma, but the tumor microenvironment is increasingly recognized as crucial to sustaining malignant B-cell survival and growth, subclonal evolution, and drug resistance. The tumor niche is made up of a dynamic and organized network of strongly heterogeneous immune and stromal cell subsets characterized by specific phenotypic, transcriptomic, and functional features. Nonmalignant cell recruitment and plasticity are dictated by lymphoma B cells, which convert their surrounding microenvironment into a supportive niche. In addition, they are also influenced by the crosstalk between the various components of this niche. In agreement with this, the B-cell lymphoma subtype is a key determinant of the organization of the tumor niche, but genetic alteration patterns, tumor localization, stage of the disease, and treatment strategy may also modulate its composition and activity. Moreover, the complex set of bidirectional interactions between B cells and their microenvironment has been proposed as a promising therapeutic target with the aim of reinforcing antitumor immunity and/or of abbrogating the lymphoma-promoting signals delivered by the tumor niche.