Summary:
Lymphomas are malignant neoplasms composed of monoclonal proliferations of
lymphocytes, which proliferate autonomously and uncontrollably, over-running
the normal lymphocytic population. Lymphomas occur within lymphoid organs-such
as lymph nodes, spleen and the mucosa-associated lymphoid tissue (MALT)-where
complex cell-cell interactions normally take place during the immune response.
B-cell non-Hodgkin lymphomas (B-NHL) represent the most common malignant
lymphoid neoplasms due to (at least) a disruption of the different phases of
normal B-cell development. MALT lymphomas, are derived from marginal zone cells
and constitute a group of low malignancy B-lymphomas with particular clinical,
histological, immunohistochemical and molecular characteristics. At the same
time, their dynamic relationship with their microenvironment is well studied,
with the Hp-positive gastric MALT lymphoma as a «pilot».
It is known that cells grow within defined environmental niches and are subject
to microenvironmental control. Outside of their niche normal cells lack
appropriate survival signals. However, during tumor development and
progression, malignant cells escape the local tissue control and escape death.
A bidirectional relationship is initiated between tumor cells and their
microenvironment, favoring tumor growth and progression.
Evidence suggests that dynamic and bidirectional feedback processes between
cancer cells and a complex network of reactive cells in their microenvironment
play a critical role during different developmental stages of most malignancies
and their progression. This network consists of a heterogeneous group of cells,
including macrophages, folliucular dendritic cells (FDCs), follicular reticular
cells (FRCs), fibroblasts, T-lymphocytes, immature myeloid cells and
endothelial cells, with further complexity being added by the extracellular
matrix scaffolding.
The complex communications between the cell populations involves interplay
between chemokines, chemokine receptors and adhesion molecules, and the balance
between these determines whether there is a tumour cell growth promotion or
inhibition.
The demonstration of the importance of the microenvironment in B-NHL has been
shown recently using methodologies such as gene expression profiling (GEP),
which have emphasized the roles of the various components of the
microenvironment.
Future treatment strategies must take into account the interactions of the
lymphoma microenvironment with the neoplastic cells, rather than only
concentrating on the latter cells. As such, the microenvironment of B-cell
lymphomas represents a challenge to the development of therapeutic agents,
requiring re-direction and inclusion of these non-neoplastic supportive cells
into future treatment strategies.
Keywords:
MALT lymphoma, microenvironment, B-NHL, targeted therapy, complex network
