Tumor-Associated Macrophages as Major Immunosuppressive Cells in the Tumor Microenvironment
Cancers,
Год журнала:
2024,
Номер
16(19), С. 3410 - 3410
Опубликована: Окт. 8, 2024
Within
the
tumor
microenvironment,
myeloid
cells
constitute
a
dynamic
immune
population
characterized
by
heterogeneous
phenotype
and
diverse
functional
activities.
In
this
review,
we
consider
recent
literature
shedding
light
on
increasingly
complex
biology
of
M2-like
immunosuppressive
tumor-associated
macrophages
(TAMs),
including
their
contribution
to
cell
invasion
metastasis,
stromal
remodeling
(fibrosis
matrix
degradation),
suppressive
functions,
in
microenvironment
(TME).
This
review
also
delves
into
intricate
signaling
mechanisms
underlying
polarization
macrophage
phenotypes,
plasticity.
We
development
promising
therapeutic
approaches
target
these
populations
cancers.
The
expanding
knowledge
distinct
subsets
TAMs,
contributions
tumorigenesis
has
sparked
significant
interest
among
researchers
regarding
potential
TAM
depletion
or
phenotypic
modulation.
Язык: Английский
Targeting tumor-associated macrophages in colon cancer: mechanisms and therapeutic strategies
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Март 21, 2025
Colon
cancer
(CC)
remains
a
primary
contributor
to
cancer-related
fatalities
worldwide,
driven
by
difficulties
in
early
diagnosis
and
constrained
therapeutic
options.
Recent
studies
underscore
the
importance
of
tumor
microenvironment
(TME),
notably
tumor-associated
macrophages
(TAMs),
fostering
malignancy
progression
therapy
resistance.
Through
their
inherent
plasticity,
TAMs
facilitate
immunosuppression,
angiogenic
processes,
metastatic
spread,
drug
tolerance.
In
contrast
M1
macrophages,
which
promote
inflammatory
tumoricidal
responses,
M2
support
expansion
dissemination
exerting
immunosuppressive
pro-angiogenic
influences.
Consequently,
manipulating
has
emerged
as
potential
avenue
enhance
treatment
effectiveness.
This
review
outlines
origins,
polarization
states,
functions
CC,
highlights
role
driving
advancement,
surveys
ongoing
efforts
target
these
cells
for
better
patient
outcomes.
Emerging
strategies
aimed
at
modulating
TAM
-
including
depletion
strategies,
reprogramming
approaches
that
shift
M2-polarized
toward
an
phenotype,
inhibition
key
signaling
pathways
sustaining
TAM-mediated
immunosuppression-are
currently
under
active
investigation.
These
hold
promise
overcoming
induced
resistance
improving
immunotherapeutic
efficacy
CC.
Язык: Английский
Research progress of tumor-associated macrophages in immune checkpoint inhibitor tolerance in colorectal cancer
World Journal of Gastrointestinal Oncology,
Год журнала:
2024,
Номер
16(10), С. 4064 - 4079
Опубликована: Сен. 25, 2024
The
relevant
mechanism
of
tumor-associated
macrophages
(TAMs)
in
the
treatment
colorectal
cancer
patients
with
immune
checkpoint
inhibitors
(ICIs)
is
discussed,
and
application
prospects
TAMs
reversing
tolerance
ICIs
are
discussed
to
provide
a
reference
for
related
studies.
As
class
drugs
widely
used
clinical
tumor
immunotherapy,
can
act
on
regulatory
molecules
cells
that
play
an
inhibitory
role-immune
checkpoints-and
kill
tumors
form
response
by
activating
variety
system.
sensitivity
different
types
ICI
varies
greatly.
phenotype
function
microenvironment
closely
efficacy
ICIs.
regulate
phenotypic
TAMs,
also
affect
therapy.
important
role
resistance,
making
full
use
this
target
as
therapeutic
strategy
expected
improve
immunotherapy
prognosis
cancer.
Язык: Английский
Multi-omic profiling of breast tumor microenvironment uncovers a role of mitochondrial calcium gatekeepers
Journal of Cancer,
Год журнала:
2024,
Номер
15(12), С. 3663 - 3674
Опубликована: Янв. 1, 2024
In
this
study,
we
aimed
to
elucidate
the
role
of
mitochondrial
calcium
uptake
1/2
(MiCU1/2)
in
breast
cancer
(BRCA)
by
employing
a
comprehensive
multi-omics
approach.Unlike
previous
research,
utilized
novel
web
application
tailored
for
whole
tumor
tissue,
single-cell,
and
spatial
transcriptomics
analysis
investigate
association
between
MiCU1/2
immune
microenvironment
(TIME).Our
gene
set
enrichment
(GSEA)
provided
insights
into
primary
biological
effects
MiCU1/2,
while
our
CRISPR-based
drug
screening
repository
identified
potential
effective
drugs.Our
study
revealed
that
high
expression
serves
as
an
independent
diagnostic
biomarker,
correlating
with
advanced
clinical
status
indicating
poorer
recurrence-free
survival
(RFS)
rates
BRCA
patients.Additionally,
transcriptome
highlighted
heightened
tumors
its
relevance
surrounding
cells.Furthermore,
using
CIBERSORT
algorithm,
discovered
positive
correlation
levels
macrophage
infiltration,
underscoring
their
impact
on
infiltration.We
also
patterns
immune-related
genes
associated
responses
against
various
cell
types,
including
CXCL,
MIF,
GDF,
SPP1,
IL16.Finally,
pharmacogenomic
small
molecule
drugs
capable
effectively
targeting
cells
elevated
expression.Overall,
establishes
promising
biomarker
diagnosis
prognostic
prediction,
well
therapeutic
target,
highlighting
importance
exploring
these
pathways
advance
patient
care
outcomes
treatment.
Язык: Английский
Identification of potential drug targets for amyotrophic lateral sclerosis by Mendelian randomization analysis based on brain and plasma proteomics
Ni Yang,
Liangyuan Shi,
Pengfei Xu
и другие.
Experimental Gerontology,
Год журнала:
2024,
Номер
195, С. 112538 - 112538
Опубликована: Авг. 9, 2024
Amyotrophic
lateral
sclerosis
as
a
fatal
neurodegenerative
disease
currently
lacks
effective
therapeutic
agents.
Thus,
finding
new
targets
to
drive
treatment
is
necessary.
In
this
study,
we
utilized
brain
and
plasma
proteins
genetic
instruments
obtained
from
genome-wide
association
studies
conduct
Mendelian
randomization
analysis
identify
potential
drug
for
amyotrophic
sclerosis.
Additionally,
validated
our
results
externally
using
other
datasets.
We
also
used
Bayesian
co-localization
phenotype
scanning.
Furthermore,
constructed
protein-protein
interaction
network
elucidate
correlations
between
the
identified
existing
targets.
indicated
that
elevated
levels
of
ANO5
(OR
=
1.30;
95
%
CI,
1.14–1.49;
P
1.52E-04),
SCFD1
3.82;
2.39–6.10;
2.19E-08),
SIGLEC9
1.05;
95%
1.03–1.07;
4.71E-05)
are
associated
with
an
increased
risk
sclerosis,
external
validation
supporting
these
findings.
Co-localization
confirmed
ANO5,
SCFD1,
(coloc.abf-PPH4
0.848,
0.984,
0.945,
respectively)
shared
same
variant
further
substantiating
role
target.
There
interactive
relationships
Our
findings
suggested
connected
might
be
promising
However,
exploration
necessary
fully
understand
underlying
mechanisms
involved.
Язык: Английский
Siglecs as modulators of macrophage phenotype and function
Seminars in Immunology,
Год журнала:
2024,
Номер
73, С. 101887 - 101887
Опубликована: Май 1, 2024
Язык: Английский
ST6GAL1-mediated sialyl linkage switching in tumor-associated macrophages drives cancer-promoting nanotubes carrying α2,6-sialylation in anti-inflammatory cells
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 3, 2024
Abstract
Tumor-associated
macrophages
(TAMs)
form
functionally
diverse
populations
of
innate
immune
cells
in
the
tumor
microenvironment
(TME).
Pro-
and
anti-inflammatory
TAMs
are
central
to
cancer
progression
by
shaping
inflammation
(im)balance,
but
it
remains
unknown
if
polarization-induced
remodeling
TAM
glycocalyx
critical
for
cellular
communication
occurs
within
TME.
Taking
a
systems
glycobiology
approach,
we
here
firstly
used
cell
surface-focused
glycomics
lectin
flow
cytometry
ex
vivo
polarized
monocyte-derived
demonstrate
profound
sialyl
linkage
switching
surface
N
-glycome
pro-inflammatory
(α2,3-sialo-favored)
(α2,6-sialo-dominant)
macrophages.
In
contrast,
no
alterations
sialylation
were
observed
O
-glycome.
ST6GAL1
that
modifies
-glycans
with
α2,6-sialylation
was
elevated
compared
levels
providing
mechanistic
basis
switching,
which
supported
silencing.
Interestingly,
SNA-focused
cytochemistry
revealed
dense
networks
dynamic
α2,6-sialylated
protein-based
nanotubules
forming
inter-connecting
structures
absent
Temporal
silencing
caused
nanotubule
disintegration
as
evidenced
SNA
biotin
fluorescence
microscopy.
Moreover,
live
recordings
cultured
without
colorectal
(CRC)
showed
reduced
macrophage
motility,
attenuated
inter-macrophage
macrophage-CRC
interactions
diminished
CRC
proliferation
upon
disruption
indicating
functional
roles
nanotubules.
Finally,
recapitulated
pro-
from
tissues
patients
advanced
CRC.
We
report
on
consequences
accompanying
polarization.
Язык: Английский
Association of SIGLEC9 Expression with Cytokine Expression, Tumor Grading, KRAS, NRAS, BRAF, PIK3CA, AKT Gene Mutations, and MSI Status in Colorectal Cancer
Current Issues in Molecular Biology,
Год журнала:
2024,
Номер
46(12), С. 13617 - 13646
Опубликована: Ноя. 29, 2024
SIGLEC9
(sialic
acid-binding
Ig-like
lectin
9)
is
a
molecule
thought
to
have
significant
influence
on
the
immune
properties
of
colorectal
cancer
(CRC)
tumor
microenvironment
(TME).
In
our
study,
we
assessed
expression
protein
in
CRC
tissue
and
surgical
margin
tissue.
Using
RT-PCR,
analyzed
mutations
KRAS,
NRAS,
BRAF,
PIK3CA,
AKT
genes.
We
observed
significantly
elevated
compared
control
group.
No
differences
were
depending
genes
or
microsatellite
instability
(MSI)
status.
However,
found
higher
high-grade
tumors
low-grade
was
associated
with
multiple
cytokines,
chemokines,
growth
factors
TME.
These
associations
suggest
potential
as
that
plays
crucial
role
shaping
TME,
well
its
therapeutic
relevance,
particularly
group
tumors.
Язык: Английский