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
Mathematical modeling and Hopf bifurcation analysis of tumor macrophage interaction with polarization delay
Journal of Biological Dynamics,
Год журнала:
2025,
Номер
19(1)
Опубликована: Май 26, 2025
Macrophages
have
both
anti-tumor
and
pro-tumor
effects.
Time
delay
is
commonly
observed
in
real
systems,
yet
its
impact
on
tumor-macrophage
dynamics
remains
unclear.
This
paper
develops
a
new
model
with
time
delay.
The
describes
the
interactions
between
tumor
cells
(T),
classically
activated
macrophages
(M1),
alternatively
(M2),
inactive
(M0).
system's
solution
computed,
equilibrium
stability
analyzed.
existence
of
Hopf
bifurcation
subsequently
established.
There
exists
bifurcating
periodic
solutions
near
internal
equilibrium,
showing
can
coexist
long
term,
as
well
potential
for
relapse.
Furthermore,
normal
form
center
manifold
theorem
are
utilized
to
study
nature
bifurcation.
Sensitivity
analysis
highlights
effect
parameters
population
dynamics.
Numerical
simulations
validate
theory,
elaborating
serve
useful
tool
system
analysis.
Язык: Английский
Regulation and Function of Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): The Role of the SRIF System in Macrophage Regulation
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(11), С. 5336 - 5336
Опубликована: Июнь 1, 2025
Colorectal
cancer
(CRC)
remains
the
leading
cause
of
morbidity
and
mortality
for
both
men
women
worldwide.
Tumor-associated
macrophages
(TAMs)
are
most
abundant
immune
cells
in
tumor
microenvironment
(TME)
solid
tumors,
including
CRC.
These
found
pro-inflammatory
M1
anti-inflammatory
M2
forms,
with
latter
increasingly
recognized
its
tumor-promoting
phenotypes.
Many
signaling
molecules
pathways,
AMPK,
EGFR,
STAT3/6,
mTOR,
NF-κB,
MAPK/ERK,
HIFs,
involved
regulating
TAM
polarization.
Consequently,
researchers
investigating
several
potential
predictive
prognostic
markers,
novel
TAM-based
therapeutic
targets,
especially
combination
therapies
Macrophages
gastrointestinal
tract,
normal
colon
rectum,
produce
growth
hormone-releasing
inhibitory
peptide/somatostatin
(SRIF/SST)
five
SST
receptors
(SSTRs,
SST1-5).
While
immunosuppressive
function
SRIF
system
is
primarily
known
various
tissues,
role
within
CRC-associated
TAMs
underexplored.
This
review
focuses
on
following
three
aspects
TAMs:
first,
rectum
broader
context
macrophage
biology;
second,
bioactive
factors
pathways
associated
function,
along
strategies
targeting
CRC;
third,
interaction
between
tissues
CRC
microenvironment.
Язык: Английский
Inosine Prevents Colorectal Cancer Progression by Inducing M1 Phenotypic Polarization of Macrophages
Molecules,
Год журнала:
2024,
Номер
30(1), С. 123 - 123
Опубликована: Дек. 31, 2024
Inosine
(IS)
is
a
naturally
occurring
metabolite
of
adenosine
with
potent
immunomodulatory
effects.
This
study
investigates
the
effects
inosine,
particularly
its
ability
to
inhibit
development
colorectal
cancer
(CRC)
cells
CT26
through
modulation
macrophage
phenotypes.
Aside
from
already
reported
inosine
on
T
cells,
in
this
study,
vitro
experiments
revealed
that
could
modulate
phenotype.
The
M1/M2
polarization
were
investigated
at
cellular
level.
Its
role
regulating
CRC
proliferation
and
migration
was
further
examined.
In
addition,
tumor
mouse
model
established
assess
mechanism
action
by
weight
measurement,
immunohistochemistry,
immunofluorescence.
significantly
increased
M1
markers
CD86
iNOS
enhanced
anti-tumor
activity
macrophages,
effectively
inhibiting
progression
metastasis
potential.
vivo,
had
significant
inhibitory
activity.
It
also
reduced
expression
Ki-67
promoted
macrophages.
Язык: Английский