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Pathogenesis of follicular lymphoma
Robert Kridel, … , Laurie H. Sehn, Randy D. Gascoyne
Robert Kridel, … , Laurie H. Sehn, Randy D. Gascoyne
Published October 1, 2012
Citation Information: J Clin Invest. 2012;122(10):3424-3431. https://doi.org/10.1172/JCI63186.
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Review Series Article has an altmetric score of 4

Pathogenesis of follicular lymphoma

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Abstract

The hallmark t(14;18)(q32;q21) in follicular lymphoma (FL) results in constitutive overexpression of the BCL2 protein, allowing B cells to abrogate the default germinal center apoptotic program. Most tumors are characterized by recurrent secondary genetic alterations including genomic gains, losses, and mutations, some providing a growth advantage, including alterations in MLL2, EPHA7, TNFRSF14, and EZH2. The sequence in which these events occur and how they contribute to progression and ultimately to transformation is unclear. Lastly, crosstalk between neoplastic B cells and non-neoplastic immune and stromal cells in the microenvironment plays an important role in sustaining tumor cell growth, cultivating immune privilege, and promoting transformation.

Authors

Robert Kridel, Laurie H. Sehn, Randy D. Gascoyne

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Figure 1

A model of the microenvironment in FL.

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A model of the microenvironment in FL.
Tumor cells are nurtured by a var...
Tumor cells are nurtured by a variety of cells (orange) such as FTH cells, FDCs, and follicular reticular cells (FRCs). Beneficial signals for growth and survival include cytokines such as IL-4 and IL-21, which bind to interleukin receptors on lymphoma cells (IL-4R/IL-21R) or CXCL12 and CXCL13 secreted by stromal cell subsets. BCR signaling occurs through stimulation of the BCR by the innate immune system through N-glycans or by specific antigen presentation through professional APCs such as FDCs. Tumor cells subvert the antitumor immune response from T helper cells, CTLs, and macrophages (purple). For example, FL cells prevent lysis through CTLs by inducing a T cell immunologic synapse dysfunction, or by secretion of IL-12 they induce T cell exhaustion. Immune cell subsets that suppress an efficient immunological response against the tumor include Tregs and M2 polarized macrophages (TAMs) (blue). The former are enriched in the FL microenvironment and dampen the T cell response. FL contributes to the preferential conversion of T helper cells into Tregs by proteins such as TGF-β or CCL22. Whereas classically activated TAMs (M1 polarized) control malignant growth through induction of a Th1 response, M2-polarized TAMs exert a tumor-promoting function through angiogenesis and induction of an immunosuppressive Th2 response.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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