The role of tumor-associated macrophage in breast cancer biology.
2018
Breast cancer is the most commonly
diagnosed malignant tumor in women worldwide and
contributes significantly as the primary cause of female
cancer related mortality. Hence, research is focused on
discovering new and effective treatment targets. The
breast tumor microenvironment (TME) comprising of
recruited host stromal cells and tumor cells, has recently
emerged as an important player in tumor progression,
with the potential for future treatment. The TME
comprises immune system elements (such as
macrophages and lymphocytes), cells composing blood
vessel, fibroblast, myofibroblast, mesenchymal stem
cells, adipocytes and extracellular matrix (ECM).
Among these cells, tumor-associated macrophages
(TAM) are the prominent components of TME in breast
cancers. Macrophages exhibit a high plasticity in
response to various external signals and participate in
innate and adoptive immune responses to control
numerous factors of TME. Depending on the
microenvironmental signal present, macrophages are
polarized into two distinct phenotypes, the classically
activated (M1) or the alternative activated (M2)
macrophages. Tumor-associated macrophages (TAMs)
closely resemble the M2-polarized. Clinicopathological
studies have suggested that TAM accumulation in
tumors correlates with a poor clinical outcome. In
human breast carcinomas, high TAM density correlates
with poor prognosis. Over the years, studies into the role
of TAMs in breast cancer progression have identified
TAMs to be capable of inducing angiogenesis,
remodelling the tumor extracellular matrix to aid
invasion, modelling breast cancer cells to evade host
immune system and recruiting immunosuppressive
leukocytes to the tumor microenvironment. Along with
these functions, the potential role for TAMs in activation
of breast cancer stem cells (CSC) has also emerged.
Thus, TAMs in breast cancer can enhance cancer cell
invasion by degrading the ECM, stimulate tumor
vascularization and angiogenesis and suppress the antitumor
functions of cytotoxic T cells resulting in poor
prognosis for patients. These observations make TAMs
an attractive target for therapeutic intervention by
targeting various aspects of their function. This review
discusses the mechanisms responsible for TAM
recruitment and highlights the roles of TAMs in
regulating tumor angiogenesis, invasion, metastasis,
immunosuppression, and chemotherapeutic resistance.
Finally, the potential for TAM-targeted therapy as a
promising novel strategy is also discussed.
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