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0:04
We have now had angiogenesis
and osteolysis.
The next thing is the impact
on immune suppression.
Myeloma cells are
known to induce
immune suppression by either
enhancing the activity
of myeloid-derived
suppressor cells or by
enhancing the activity of
tumor-associated macrophages.
So the same questions
arise again.
Do EVs play a role?
What is the cargo, and does
hypoxia enhance this effect?
0:32
Just to give you
some background,
myeloid-derived
suppressor cells are
a heterogeneous
population of cells
originating from myeloid
progenitor cells
in the bone marrow, which
remain undifferentiated.
They accumulate in the
tumor microenvironment
and they suppress
the immune system
by activating T-regs,
or regulatory T-cells,
and by secreting
suppressive cytokines.
You can divide these
MDSCs into either
monocytic MDSCs or
granulocytic MDSCs.
The monocytic MDSCs are
the most suppressive.
MDSC activation is usually
triggered by
activation of STAT3.
Now these MDSCs
also play a role in
angiogenesis, metastasis
and stimulate myeloma
proliferation.
1:21
Just to show you how
myeloma increases
the number of MDSCs,
we compared healthy
mice to myeloma mice
and then we looked at the
number of CD11b cells.
This is what we did
in panel A, and then
we further divided the MDSCs
based on their phenotype.
We either have
the Ly6G^low
Ly6C^intermediate phenotype,
which represents the
monocytic MDSCs or we have
the Ly6G^high
Ly6C^intermediate phenotype
which represents the
granulocytic MDSCs.
You can see that in a
myeloma bone marrow
there is an increase in
the monocytic MDSCs,
so the most immune suppressive.
What we then did is like what
we did for the osteolysis.
We treated healthy mice
with just the EVs.
Not with the myeloma
cells, just the EVs.
Also here we saw an
increase in spleen size.
But when looking at CD11bs,
we saw an increase in both
bone marrow and spleen.
What was interesting
is when we looked at
the phenotype of these MDSCs,
we saw a similar phenotype
as when we would
have injected the mice with
myeloma cells themselves.
We saw an increase in the
Ly6G^low Ly6C^intermediate type
and a reduction in Ly6G^high
Ly6C^intermediate,
both in bone marrow and spleen.
