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Printable Handouts
Navigable Slide Index
- Introduction
- Tumor microenvironment is a complex system
- Myeloid cells in cancer exist in two functional states
- Myeloid cells are associated with bad clinical outcome in cancer
- How myeloid cells developed in pathological conditions
- The transcriptional trajectory of neutrophils development
- Tumor associated macrophages and MDSC regulate tumor progression
- Regulation of MDSC development
- Two-signal concept of MDSC development
- Phenotype of MDSC in comparison to neutrophils and monocytes
- Surface markers and genes associated with MDSC
- Immunosuppressive activity of MDSC
- Gene expression profile of macrophages
- Suppressive activity of macrophages (humans)
- Suppressive activity of macrophages (mice)
- Adoptive transfer
- S100A9 expression in macrophages
- Effect of S100A9 on suppressive activity
- Melanoma patients treated with PD1 antibody
- Heterogeneity of neutrophils in cancer
- Three populations of neutrophils in cancer
- Different dynamic of PMN-MDSC accumulation
- Activated tumor PMN-MDSC are highly suppressive
- Trajectory analysis
- Clinical relevance of tumor PMN-MDSC signature
- Populations of human neutrophils
- Balance of power in MDSC regulation
- IFNAR1 is downregulated in MDSCs
- Absence of IFNAR1 is not enough to convert neutrophils to PMN-MDSC
- IFN1 signaling is involved in negative regulation of MDSC
- MDSC suppressive activity is abrogated in SA mice
- Ferroptosis
- Tumor neutrophils demonstrated enrichment for ferroptosis related genes
- Enrichment for ferroptosis signature in tumor PMN
- Accumulation of oxidized PE in tumor PMN
- Ferroptosis susceptibility
- Ferroptosis induction converted PMN to PMN-MDSC
- Suppressive activity of tumor but not spleen PMN-MDSC is controlled by ferroptosis
- Inhibition of ferroptosis resulted in decreased tumor progression
- Pharmacological induction of ferroptosis promoted tumor growth
- Ferroptosis signature in cancer patients
- Myeloid cells at the center of therapeutic effort
- Approaches to target myeloid cells in cancer
- How can we use myeloid cell targeting
- Multiple approaches to target myeloid cells in cancer
- Thank you
Topics Covered
- Myeloid cells in cancer
- Tumor associated macrophages and MDSC regulate tumor progression
- Immunosuppressive activity of MDSC
- Effect of S100A9 on suppressive activity
- IFNAR1 is downregulated in MDSCs
- Ferroptosis
- Approaches to target myeloid cells in cancer
Links
Series:
- The Immune System - Key Concepts and Questions
- Immunotherapy of Cancer
- Macrophage Heterogeneity and Function
Categories:
Therapeutic Areas:
Talk Citation
Gabrilovich, D. (2024, February 29). Myeloid-derived suppressor cells in cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/RXZP5320.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Gabrilovich is an employee and stakeholder of AstraZeneca, however no products of AstraZeneca or any other companies are discussed.
Other Talks in the Series: The Immune System - Key Concepts and Questions
Other Talks in the Series: Immunotherapy of Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Dmitry Gabrilovich
and for many years, I was
an academic researcher,
professor at different
institutions
working on myeloid cell biology.
For the last three
and a half years,
I am the Executive Director and
Chief Scientist at AstraZeneca,
where I'm continuing working on
basic and translational aspect
of myeloid cell biology,
specifically myeloid-derived
suppressor cells.
I will be discussing
with you today
the basic biology of
myeloid cells in cancer,
especially myeloid-derived
suppressor cells,
and really illustrate
their biology
with several examples
of our recent studies.
0:38
Tumor microenvironment is
full of myeloid cells.
They represent one
of the major part
of this microenvironment.
Myeloid cells in cancer
are largely represented by
tumor associated macrophages
and neutrophils and monocytes,
and specifically their
pathological state of activation,
myeloid-derived suppressor cells
from which I will be
discussing a little bit later.
There's also dendritic
cells present in tumors.
The main message, what we
learned in the last
several decades
is that practically all tumors
are infiltrated
with myeloid cells.
There is no such thing as
a cold tumor in respect
of myeloid cells.
They play a major role
in the regulation of
immune responses in
cancer and promoting
tumor progression through
non-immunological means,
meaning affecting angiogenesis,
extracellular matrix,
and many other things.
As I said, myeloid
cells represent
very diverse group of cells with
multiple different
functionalities
and they produce multiple
different factors.
From the long time,
the question was:
what defines the functions
of these myeloid
cells in cancer?
That is myeloid cells really
exist to regulate tumor
because in evolution,
these cells
are one of our major
protectors from pathogens.
So why these things
changed in cancer?
That's what we try
to figure out for
the last 20 years
and we come up with
a clear and
functional hypothesis
which has been confirmed
in many different studies,
but still under debate,
which I will discuss
with you right now.