Pathogenesis of follicular lymphoma

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.

Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8+T cells

“…36,37 Infiltration of CD4 + and T reg cells has previously been reported in some studies to correlate with improved outcome. 31,32 Because FL can spontaneously regress or remit, 5 and in some cases vaccination approaches are effective, 6 it will be very important in the future to characterize more precisely the immune milieu of individual patients to better define those who may be more likely to respond to immune-based therapies, such as checkpoint blockade therapies with anti-PD-1 or anti-CTLA-4 antibodies, anti-idiotype vaccines, and, possibly in the future, adoptive cell therapy.…”

Lectin-like transcript 1 is a marker of germinal center-derived B-cell non-Hodgkin's lymphomas dampening natural killer cell functions

“…13 In NHL patients, our understanding of the role of the microenvironment in the maintenance of B-cell lymphomas is increasing steadily. [14][15][16][17] Host immunity is often suppressed or diverted by lymphoma cells. Several mechanisms have been identified which lead to inefficient antitumor responses.…”

Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation

“…FL frequently responds to a variety of therapies, including monoclonal antibodies, cytotoxic chemotherapeutic agents, and radiotherapy. However, most relapse after sequential regimens and have a cumulatively higher risk for eventual histological transformation to a higher grade of malignancy (4). These relapses frequently occur through a process of divergent evolution, originating from tumor cell progenitors that contain only an early-occurring subset of the mutations found in evolved tumor cells (5).…”