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0:00
Hi.
My name is Dimitry Gabrilovich.
I am head of the Tumor Immunology
Program in Wistar Institute
and Professor to University of
Pennsylvania in Philadelphia.
I am going to talk to you about
myeloid-derived suppressor
cells in tumors.
0:16
What we'll discuss, the
following topics today.
First, we will discuss a definition
of myeloid-derived suppressor
cells, then the main
characteristics, followed
by molecular mechanisms regulating
myeloid-derived suppressor cell
expansion, and mechanism of
myeloid-derived suppressor cell
activity, primarily, the
inhibitory effect on T cells.
We will talk about
therapeutic targeting
of myeloid-derived
suppressor cells in cancer
at the end of the presentation.
0:45
Myeloid cells with
immunosuppressive features
have been known since the late '70s.
Investigators describe appearances
of these cells in response
to stimulation with
different growth factors.
The first evidence that these
cells could be involved in tumor
development or associated
with the tumor development
have been recorded in mid-90s.
And they become the focus of more
intensive studies in early 2000.
The term of myeloid-derived
suppressor cells
has been introduced in 2007.
And these days, these cells
become the focus of intensive studies
by many groups in different
conditions, primarily in cancer.
1:29
As we know, myeloid cells
differentiate in bone marrow
through the sequential
steps involved
in several different progenitors
from hematopoietic stem cells
through the common
myeloid progenitors,
and they end up in
three major classes
of terminally differentiated
mature myeloid cells, neutrophils,
or granulocytes, some
macrophages, or dendritic cells.
In cancer, tumor and
tumor-associated stroma
produce multiple different
cytokines which dramatically
affect differentiation
of myeloid cells.
The end result of this
process is accumulation,
in some cases, dramatic
accumulation, of cells which are
characterized myeloid lineages,
but also, the relatively immature
phenotype and a very
important ability
to suppress immune
function; therefore,
the cell, so-called
myeloid-derived suppressor cells.
And I will refer to them as MDSC
for simplicity in the next slides.
