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Hello, my name is Michele De Palma,
and I'm group leader at the Angiogenesis and Tumor Targeting
Unit of the San Raffaele Scientific Institute in Milan.
I've been appointed recently as the assistant professor at the ISRED Institute in Lausanne.
Mario Leonardo Squadrito, a PhD student in my lab,
has contributed to the writing of this talk on tumor-associated macrophages.
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Tumors are like complex organs that arise from normal tissues.
They are not only made of transformed malignant cells,
but also contain a vast assortment of non-transformed cells,
which make up the so called, tumor stroma.
The tumor stroma comprises of blood vessels,
which provide oxygen and nutrients to the growing tumor mass,
fibroblasts, which together with the tumor cells,
produce several components of the extracellular matrix,
and a variety of infiltrating cells of hematopoietic origin, also known as leukocytes.
As shown in panels A,
the normal non-transformed breast and prostate tissues contain sparse leukocytes.
The majority of these cells represent tissue raised in macrophages.
As shown in panels B,
the malignant breast and prostate are heavily infiltrated by leukocytes,
clearly outnumbering those present in the normal breast and prostate tissue.
Of these tumor-associated leukocytes,
a substantial fraction is represented by tumor-associated macrophages.
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Tumor-associated macrophages are present in distinct tumor microenvironments.
For example, they are often very abundant in
the stromal areas made of connective tissue that surround the tumor nodules.
Macrophages are also found in close proximity to blood vessels,
both in stromal and tumor cell areas.
Another tumor microenvironment where macrophages generally
accumulate are the peri-necrotic or hypoxic tumor areas.
Low oxygen tension, also known as hypoxia,
stimulates the tumor cells to express several monocyte macrophage chemoattractants.
This promotes monocyte recruitment and macrophage accumulation
in both mouse and human tumors.
Once recruited, macrophages are retained in hypoxic tumor areas
due to abrogation of chemotactic signal transduction,
and downregulation of chemoattractant receptors.
Hypoxia then enhances the expression of
several proangiogenic and protumoural factors in the macrophages,
by activating hypoxia-inducible factors.
