Small,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 10, 2025
Abstract
Glioblastoma
(GBM),
the
most
malignant
brain
tumor
with
high
prevalence,
remains
highly
resistant
to
existing
immunotherapies
due
significant
immunosuppression
within
microenvironment
(TME),
predominantly
manipulated
by
M2‐phenotypic
tumor‐associated
macrophages
(M2‐TAMs).
Here
in
this
work,
an
M2‐TAMs
targeted
nano‐reprogrammers,
MG5‐S‐IMDQ,
is
established
decorating
mannose
molecule
as
targeting
moiety
well
toll‐like
receptor
(TLR)
7/8
agonist,
imidazoquinoline
(IMDQ)
on
dendrimeric
nanoscaffold.
MG5‐S‐IMDQ
demonstrated
excellent
capacity
of
penetrating
blood‐brain
barrier
(BBB)
selectively
GBM
microenvironment,
leading
a
phenotype
transformation
and
function
restoration
TAMs
shown
heightened
phagocytic
activity
toward
cells,
enhanced
cytotoxic
effects,
improved
antigen
cross‐presentation
capability.
In
meantime,
induction
function‐oriented
“gear
effect”,
treatment
extended
its
impact
systemically
enhancing
infiltration
type
I
conventional
dendritic
cells
(cDC1s)
into
sites
bolstering
adaptive
immune
responses.
sum,
precisely
working
unique
target
situ,
nano‐reprogrammers
successfully
robust
network
that
worked
synergistically
combat
tumors.
This
facile
nanoplatform‐based
immunomodulatory
strategy,
serving
powerful
convenient
monotherapy
or
complementary
alongside
other
therapies
like
surgery,
provided
deep
insights
for
advancing
translational
study
GBM.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Oct. 18, 2024
Immunotherapy
has
made
significant
strides
in
cancer
treatment,
particularly
through
immune
checkpoint
blockade
(ICB),
which
shown
notable
clinical
benefits
across
various
tumor
types.
Despite
the
transformative
impact
of
ICB
treatment
therapy,
only
a
minority
patients
exhibit
positive
response
to
it.
In
with
solid
tumors,
those
who
respond
well
typically
demonstrate
an
active
profile
referred
as
"hot"
(immune-inflamed)
phenotype.
On
other
hand,
non-responsive
may
distinct
"cold"
(immune-desert)
phenotype,
differing
from
features
tumors.
Additionally,
there
is
more
nuanced
"excluded"
positioned
between
and
categories,
known
type.
Effective
differentiation
understanding
intrinsic
factors,
characteristics,
TME,
external
factors
are
critical
for
predicting
results.
It
widely
accepted
that
therapy
exerts
profound
effect
on
limited
efficacy
against
or
"altered"
necessitating
combinations
therapeutic
modalities
enhance
cell
infiltration
into
tissue
convert
tumors
ones.
Therefore,
aligning
traits
this
review
systematically
delineates
respective
influencing
extensively
discusses
varied
approaches
drug
targets
based
assess
efficacy.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
36(11)
Published: Dec. 14, 2023
Pyroptosis,
an
emerging
mechanism
of
programmed
cell
death,
holds
great
potential
to
trigger
a
robust
antitumor
immune
response.
Platinum-based
chemotherapeutic
agents
can
induce
pyroptosis
via
caspase-3
activation.
However,
these
also
enhance
cyclooxygenase-2
(COX-2)
expression
in
tumor
tissues,
leading
drug
resistance
and
evasion
pancreatic
cancer
significantly
limiting
the
effectiveness
chemotherapy-induced
pyroptosis.
Here,
amphiphilic
polymer
(denoted
as
PHDT-Pt-In)
containing
both
indomethacin
(In,
COX-2
inhibitor)
platinum(IV)
prodrug
(Pt(IV))
is
developed,
which
responsive
glutathione
(GSH).
This
self-assemble
into
nanoparticles
Pt-In
NP)
that
disintegrate
cells
due
GSH
responsiveness,
releasing
In
inhibit
expression,
hence
overcoming
chemoresistance
amplifying
cisplatin-induced
mouse
model,
NP
growth
elicit
innate
adaptive
responses.
Moreover,
when
combined
with
anti-programmed
death
ligand
(α-PD-L1)
treatment,
demonstrate
ability
completely
suppress
metastatic
tumors,
transforming
"cold
tumors"
"hot
tumors".
Overall,
sustained
release
Pt(IV)
from
amplifies
platinum-drug-induced
long-term
responses,
presenting
generalizable
strategy
for
cancer.
Journal of Cancer Research and Clinical Oncology,
Journal Year:
2024,
Volume and Issue:
150(5)
Published: May 7, 2024
Abstract
Background
Tumor
growth
is
closely
linked
to
the
activities
of
various
cells
in
tumor
microenvironment
(TME),
particularly
immune
cells.
During
progression,
circulating
monocytes
and
macrophages
are
recruited,
altering
TME
accelerating
growth.
These
adjust
their
functions
response
signals
from
stromal
Tumor-associated
(TAMs),
similar
M2
macrophages,
key
regulators
TME.
Methods
We
review
origins,
characteristics,
TAMs
within
This
analysis
includes
mechanisms
through
which
facilitate
evasion
promote
metastasis.
Additionally,
we
explore
potential
therapeutic
strategies
that
target
TAMs.
Results
instrumental
mediating
malignant
behaviors.
They
release
cytokines
inhibit
effector
attract
additional
immunosuppressive
primarily
T
cells,
inducing
exhaustion
directly,
influencing
activity
indirectly
cellular
interactions,
or
suppressing
checkpoints.
directly
involved
proliferation,
angiogenesis,
invasion,
Summary
Developing
innovative
tumor-targeted
therapies
immunotherapeutic
currently
a
promising
focus
oncology.
Given
pivotal
role
evasion,
several
approaches
have
been
devised
them.
include
leveraging
epigenetics,
metabolic
reprogramming,
engineering
repolarize
TAMs,
inhibiting
recruitment
activity,
using
as
drug
delivery
vehicles.
Although
some
these
remain
distant
clinical
application,
believe
future
targeting
will
offer
significant
benefits
cancer
patients.
Journal of Hematology & Oncology,
Journal Year:
2024,
Volume and Issue:
17(1)
Published: Jan. 31, 2024
The
liver
is
essential
for
metabolic
homeostasis.
onset
of
cancer
often
accompanied
by
dysregulated
function,
leading
to
rearrangements.
Overwhelming
evidence
has
illustrated
that
cellular
metabolism
can,
in
turn,
promote
anabolic
growth
and
tumor
propagation
a
hostile
microenvironment.
In
addition
supporting
continuous
survival,
disrupted
process
also
creates
obstacles
the
anticancer
immune
response
restrains
durable
clinical
remission
following
immunotherapy.
this
review,
we
elucidate
communication
between
cells
their
surrounding
discuss
how
reprogramming
impacts
microenvironment
efficacy
We
describe
crucial
role
gut-liver
axis
remodeling
crosstalk
surveillance
escape,
highlighting
novel
therapeutic
opportunities.
Advanced Science,
Journal Year:
2024,
Volume and Issue:
11(38)
Published: Aug. 5, 2024
Lactate
plays
a
critical
role
as
an
energy
substrate,
metabolite,
and
signaling
molecule
in
hepatocellular
carcinoma
(HCC).
Intracellular
lactate-derived
protein
lysine
lactylation
(Kla)
is
identified
contributor
to
the
progression
of
HCC.
Liver
cancer
stem
cells
(LCSCs)
are
believed
be
root
cause
phenotypic
functional
heterogeneity
However,
impact
Kla
on
biological
processes
LCSCs
remains
poorly
understood.
Here
enhanced
glycolytic
metabolism,
lactate
accumulation,
elevated
levels
observed
compared
HCC
cells.
H3K56la
was
found
closely
associated
with
tumourigenesis
stemness
LCSCs.
Notably,
comprehensive
examination
lactylome
proteome
ALDOA
K230/322
lactylation,
which
promoting
Furthermore,
this
study
demonstrated
tight
binding
between
aldolase
A
(ALDOA)
dead
box
deconjugate
enzyme
17
(DDX17),
attenuated
by
ultimately
enhancing
regulatory
function
DDX17
maintaining
This
investigation
highlights
significance
modulating
its
Targeting
may
offer
promising
therapeutic
approach
for
treating
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
14
Published: Jan. 29, 2024
Tumor-associated
macrophages
(TAMs)
are
present
in
almost
all
solid
tumor
tissues.
16They
play
critical
roles
immune
regulation,
angiogenesis,
stem
cell
activation,
invasion
and
metastasis,
resistance
to
therapy.
However,
it
is
unclear
how
TAMs
perform
these
functions.
With
the
application
of
single-cell
RNA
sequencing
(scRNA-seq),
has
become
possible
identify
TAM
subpopulations
associated
with
distinct
In
this
review,
we
discuss
four
novel
tumors
based
on
core
gene
signatures
by
scRNA-seq,
including
FCN1
+
,
SPP1
C1Q
CCL18
TAMs.
Functional
enrichment
expression
scRNA-seq
data
from
different
tissues
found
that
may
induce
inflammation;
potentially
involved
cancer
whereas
participate
regulation
suppression;
And
cells
terminal
immunosuppressive
not
only
have
a
stronger
function
but
also
enhance
metastasis.
can
be
further
divided
into
populations
Meanwhile,
will
emerging
evidence
highlighting
separating
macrophage
there
exist
potential
disconnects
between
types
identified
their
actual
function.
Signal Transduction and Targeted Therapy,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: March 7, 2025
Abstract
Macrophages
are
immune
cells
belonging
to
the
mononuclear
phagocyte
system.
They
play
crucial
roles
in
defense,
surveillance,
and
homeostasis.
This
review
systematically
discusses
types
of
hematopoietic
progenitors
that
give
rise
macrophages,
including
primitive
progenitors,
erythro-myeloid
stem
cells.
These
have
distinct
genetic
backgrounds
developmental
processes.
Accordingly,
macrophages
exhibit
complex
diverse
functions
body,
phagocytosis
clearance
cellular
debris,
antigen
presentation,
response,
regulation
inflammation
cytokine
production,
tissue
remodeling
repair,
multi-level
regulatory
signaling
pathways/crosstalk
involved
homeostasis
physiology.
Besides,
tumor-associated
a
key
component
TME,
exhibiting
both
anti-tumor
pro-tumor
properties.
Furthermore,
functional
status
is
closely
linked
development
various
diseases,
cancer,
autoimmune
disorders,
cardiovascular
disease,
neurodegenerative
metabolic
conditions,
trauma.
Targeting
has
emerged
as
promising
therapeutic
strategy
these
contexts.
Clinical
trials
macrophage-based
targeted
drugs,
immunotherapies,
nanoparticle-based
therapy
were
comprehensively
summarized.
Potential
challenges
future
directions
targeting
also
been
discussed.
Overall,
our
highlights
significance
this
versatile
cell
human
health
which
expected
inform
research
clinical
practice.
Advanced Materials,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 10, 2025
Abstract
Cancer
immunotherapy,
which
leverages
immune
system
components
to
treat
malignancies,
has
emerged
as
a
cornerstone
of
contemporary
therapeutic
strategies.
Yet,
critical
concerns
about
the
efficacy
and
safety
cancer
immunotherapies
remain
formidable.
Nanotechnology,
especially
polymeric
nanoparticles
(PNPs),
offers
unparalleled
flexibility
in
manipulation‐from
chemical
composition
physical
properties
precision
control
nanoassemblies.
PNPs
provide
an
optimal
platform
amplify
potency
minimize
systematic
toxicity
broad
spectrum
immunotherapeutic
modalities.
In
this
comprehensive
review,
basics
polymer
chemistry,
state‐of‐the‐art
designs
from
physicochemical
standpoint
for
encompassing
vaccines,
situ
vaccination,
adoptive
T‐cell
therapies,
tumor‐infiltrating
cell‐targeted
antibodies,
cytokine
therapies
are
delineated.
Each
immunotherapy
necessitates
distinctively
tailored
design
strategies
nanoplatforms.
The
extensive
applications
PNPs,
investigation
their
mechanisms
action
enhanced
particularly
focused
on.
profiles
clinical
research
progress
discussed.
Additionally,
forthcoming
developments
emergent
trends
nano‐immunotherapeutics
poised
transform
treatment
paradigms
into
clinics
explored.