Tumor microenvironment of follicular lymphoma

Abstract

: Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and accounts for approximately 20% of all new non-Hodgkin lymphomas in western countries. Although FL generally has an indolent natural history, a subset can transform into high-grade lymphomas such as diffuse large B-cell lymphoma (DLBCL) or progress rapidly with associated poor clinical outcomes. The development of more effective means of FL control prior to transformation or progression is likely to be key to improving results. Over the past 10–15 years there has been a rapid accumulation in studies focusing on the FL tumor microenvironment, leading to an expansion in our understanding of this complex and complicated neighbourhood. The FL microenvironment is distinct from other B cell lymphomas, with a complex interplay of cellular and non-cellular components, and plays a critical role in the pathogenesis of this disease. As part of this special series on FL, this Review covers our current knowledge of the FL tumor microenvironment with a focus on the cellular composition, key genetic aberrations, disturbances in the cytokine milieu and the neoantigen landscape of FL. We then explore the impact of the FL tumor microenvironment on risk stratification strategies and role of novel therapeutics targeting the microenvironment. Given the critical role of the microenvironment in the pathogenesis of FL, and the exciting possibility of novel therapeutic avenues, the objective of this review is to provide the reader with a summary to understand the key literature and highlight gaps in knowledge that should be prioritised in the pursuit of more effective therapies.