Role of the tumor microenvironment in mature B-cell lymphoid malignancies

Abstract

The tumor microenvironment is the cellular and molecular environment in which the tumor exists and with which it continuously interacts. In B-cell lymphomas, this microenvironment is intriguing in that it plays critical roles in the regulation of tumor cell survival and proliferation, fostering immune escape as well as the development of treatment resistance. The purpose of this review is to summarize the proceedings of the Second Annual Summit on the Immune Microenvironment in Hematologic Malignancies that took place on September 11-12, 2014 in Dublin, Ireland. We provide a timely overview of the composition and biological relevance of the cellular and molecular microenvironment interface and discuss the role of interactions between the microenvironment and neoplastic cells in a variety of B-cell lymphomas. In addition, we focus on various novel therapeutic strategies that target the tumor microenvironment, including agents that modulate B-cell receptor pathways and immune-checkpoints, chimeric antigen receptor T cells and immunomodulatory agents.

Figure 1.

Schematic diagram of the typical microenvironment of the three B-cell lymphoma subtypes that represent the extremes of the spectrum of tumor microenvironment — recruitment, re-education and effacement. These lymphoma subtypes represent the range of tumor cell content, from ~1% in cHL to typically more than 90% in BL. The other B-cell lymphomas fall within this range, as shown for the most common B-cell lymphomas (center). Typically, the ratio of malignant cells to microenvironmental cells increases across the range, from cHL to BL, as shown. DLBCL, diffuse large B-cell lymphoma; FOXP3, forkhead box protein P3; HRS, Hodgkin Reed–Sternberg; MALT, mucosa-associated lymphoid tissue; MCL, mantle cell lymphoma; T_FH, follicular T helper; T_H, T helper; T_FR, follicular regulatory T. Reproduced from Scott and Gascoyne with permission from Nature Publishing Group.