The tumour microenvironment in B cell lymphomas

Key Points B cell lymphomas show a range of extent and composition of tumour microenvironment components, partly reflecting tumour cell content and acquired genetic aberrations harboured by the lymphoma cells. B cell lymphomas home to and co-opt the tumour microenvironment to derive survival and growth signals and to achieve escape from immune surveillance. Tumour–microenvironment interactions are important contributors to both pathogenesis and prognosis of B cell lymphomas. Some aspects of treatment resistance are mediated through tumour–microenvironment interactions, via factors secreted by stromal cells in response to lymphoma cells and cell adhesion-mediated drug resistance. A fundamental understanding of tumour–microenvironment interactions underlies treatment strategies, including immune checkpoint blockade and separating lymphoma cells from their supportive microenvironment. Future studies will include overlaying the genomic aberrations in the lymphoma cells on the composition of the tumour microenvironment and will aim to determine the functional consequences of these interactions. This Review discusses the role of the tumour microenvironment in the pathogenesis of B cell lymphomas, proposing three main types of lymphoma-associated tumour microenvironment. B cell lymphomas are cancers that arise from cells that depend on numerous highly orchestrated interactions with immune and stromal cells in the course of normal development. Despite the recent focus on dissecting the genetic aberrations within cancer cells, it has been increasingly recognized that tumour cells retain a range of dependence on interactions with the non-malignant cells and stromal elements that constitute the tumour microenvironment. A fundamental understanding of these interactions gives insight into the pathogenesis of most B cell lymphomas and, moreover, identifies novel therapeutic opportunities for targeting oncogenic pathways, both now and in the future.