Abstract
Dissecting
the
spatial
heterogeneity
of
cancer-associated
fibroblasts
(CAFs)
is
vital
for
understanding
tumor
biology
and
therapeutic
design.
By
combining
pathological
image
analysis
with
proteomics,
we
revealed
two
stromal
archetypes
in
hepatocellular
carcinoma
(HCC)
different
biological
functions
extracellular
matrix
compositions.
Using
paired
single-cell
RNA
epigenomic
sequencing
Stereo-seq,
fibroblast
subsets
CAF-FAP
CAF-C7,
whose
enrichment
strongly
correlated
opposing
patient
prognosis.
We
discovered
functional
units,
one
intratumor
inflammatory
hub
featured
by
plus
CD8_PDCD1
proximity
other
marginal
wound-healing
CAF-C7
Macrophage_SPP1
co-localization.
Inhibiting
combined
anti-PD-1
orthotopic
HCC
models
led
to
improved
regression
than
either
monotherapy.
Collectively,
our
findings
suggest
stroma-targeted
strategies
based
on
defined
archetypes,
raising
concept
that
CAFs
change
their
transcriptional
program
intercellular
crosstalk
according
context.
Immunity,
Год журнала:
2023,
Номер
56(10), С. 2188 - 2205
Опубликована: Окт. 1, 2023
The
cancer-immunity
cycle
provides
a
framework
to
understand
the
series
of
events
that
generate
anti-cancer
immune
responses.
It
emphasizes
iterative
nature
response
where
killing
tumor
cells
by
T
initiates
subsequent
rounds
antigen
presentation
and
cell
stimulation,
maintaining
active
immunity
adapting
it
evolution.
Any
step
can
become
rate-limiting,
rendering
system
unable
control
growth.
Here,
we
update
based
on
remarkable
progress
past
decade.
Understanding
mechanism
checkpoint
inhibition
has
evolved,
as
our
view
dendritic
in
sustaining
anti-tumor
immunity.
We
additionally
account
for
role
microenvironment
facilitating,
not
just
suppressing,
response,
discuss
importance
considering
tumor's
immunological
phenotype,
"immunotype".
While
these
new
insights
add
some
complexity
cycle,
they
also
provide
targets
research
therapeutic
intervention.
Cancer Cell,
Год журнала:
2024,
Номер
42(3), С. 396 - 412.e5
Опубликована: Янв. 18, 2024
Despite
advances
in
treatment,
lung
cancer
survival
rates
remain
low.
A
better
understanding
of
the
cellular
heterogeneity
and
interplay
cancer-associated
fibroblasts
(CAFs)
within
tumor
microenvironment
will
support
development
personalized
therapies.
We
report
a
spatially
resolved
single-cell
imaging
mass
cytometry
(IMC)
analysis
CAFs
non-small
cell
cohort
1,070
patients.
identify
four
prognostic
patient
groups
based
on
11
CAF
phenotypes
with
distinct
spatial
distributions
show
that
are
independent
factors
for
survival.
The
presence
tumor-like
is
strongly
correlated
poor
prognosis.
In
contrast,
inflammatory
interferon-response
associated
inflamed
microenvironments
higher
High
density
matrix
low
immune
infiltration
negatively
summary,
our
data
phenotypic
features
outcome
NSCLC.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Июнь 18, 2024
Abstract
Tumorigenesis
is
a
multistep
process,
with
oncogenic
mutations
in
normal
cell
conferring
clonal
advantage
as
the
initial
event.
However,
despite
pervasive
somatic
and
expansion
tissues,
their
transformation
into
cancer
remains
rare
event,
indicating
presence
of
additional
driver
events
for
progression
to
an
irreversible,
highly
heterogeneous,
invasive
lesion.
Recently,
researchers
are
emphasizing
mechanisms
environmental
tumor
risk
factors
epigenetic
alterations
that
profoundly
influencing
early
malignant
evolution,
independently
inducing
mutations.
Additionally,
evolution
tumorigenesis
reflects
multifaceted
interplay
between
cell-intrinsic
identities
various
cell-extrinsic
exert
selective
pressures
either
restrain
uncontrolled
proliferation
or
allow
specific
clones
progress
tumors.
by
which
induce
both
intrinsic
cellular
competency
remodel
stress
facilitate
not
fully
understood.
In
this
review,
we
summarize
genetic,
epigenetic,
external
events,
effects
on
co-evolution
transformed
cells
ecosystem
during
initiation
evolution.
A
deeper
understanding
earliest
molecular
holds
promise
translational
applications,
predicting
individuals
at
high-risk
developing
strategies
intercept
transformation.
Cancer Discovery,
Год журнала:
2024,
Номер
14(8), С. 1375 - 1388
Опубликована: Авг. 2, 2024
Abstract
The
extracellular
matrix
(ECM)
is
an
abundant
noncellular
component
of
most
solid
tumors
known
to
support
tumor
progression
and
metastasis.
interplay
between
the
ECM
cancer
therapeutics
opens
up
new
avenues
in
understanding
biology.
While
protect
from
anticancer
agents
by
serving
as
a
biomechanical
barrier,
emerging
studies
show
that
various
therapies
induce
remodeling,
resulting
therapy
resistance
progression.
This
review
discusses
critical
issues
this
field
including
how
influences
treatment
outcome,
affect
challenges
associated
with
targeting
ECM.
Significance:
intricate
relationship
reveals
novel
insights
into
biology
its
effective
treatment.
may
anti-cancer
agents,
recent
research
highlights
paradoxical
role
therapy-induced
remodeling
promoting
explores
key
aspects
therapeutics.
Cancer Discovery,
Год журнала:
2023,
Номер
13(11), С. 2339 - 2355
Опубликована: Сен. 8, 2023
Abstract
The
protein
phosphatase
SHP2/PTPN11
has
been
reported
to
be
a
key
modulator
of
proliferative
pathways
in
wide
range
malignancies.
Intriguingly,
SHP2
also
described
as
critical
regulator
the
tumor
microenvironment.
Based
on
this
evidence
is
considered
multifaceted
target
cancer,
spurring
notion
that
development
direct
inhibitors
would
provide
twofold
benefit
intrinsic
and
extrinsic
inhibition.
In
review,
we
will
discuss
role
cancer
microenvironment,
clinical
strategies
which
are
leveraged
combination
agents
improve
therapeutic
response.
Significance:
functions
pleiotropic
factor,
its
inhibition
not
only
hinders
growth
but
reshapes
Although
their
single-agent
activity
may
limited,
hold
potential
being
enhance
depth
durability
response
therapy.
Theranostics,
Год журнала:
2024,
Номер
15(3), С. 993 - 1016
Опубликована: Дек. 2, 2024
Immunotherapy
has
transformed
current
cancer
management,
and
it
achieved
significant
progress
over
last
decades.
However,
an
immunosuppressive
tumor
microenvironment
(TME)
diminishes
the
effectiveness
of
immunotherapy
by
suppressing
activity
immune
cells
facilitating
immune-evasion.
Adenosine
monophosphate-activated
protein
kinase
(AMPK),
a
key
modulator
cellular
energy
metabolism
homeostasis,
gained
growing
attention
in
anti-tumor
immunity.
Metformin
is
usually
considered
as
cornerstone
diabetes
its
role
activating
AMPK
pathway
also
been
extensively
explored
therapy
although
findings
on
remain
inconsistent.
nanomedicine
formulation
found
to
hold
potential
reprogramming
TME
through
immunometabolic
modulation
both
cells.
This
review
elaborates
foundation
via
metformin-based
nanomedicines,
offering
valuable
insights
for
next
generation
therapy.
Abstract
It
is
newly
revealed
that
collagen
works
as
a
physical
barrier
to
tumor
immune
infiltration,
oxygen
perfusion,
and
depressor
in
solid
tumors.
Meanwhile,
after
radiotherapy
(RT),
the
programmed
death
ligand‐1
(PD‐L1)
overexpression
transforming
growth
factor‐β
(TGF‐β)
excessive
secretion
would
accelerate
DNA
damage
repair
trigger
T
cell
exclusion
limit
RT
efficacy.
However,
existing
drugs
or
nanoparticles
can
hardly
address
these
obstacles
of
highly
effective
simultaneously,
effectively,
easily.
In
this
study,
it
inducing
mitochondria
dysfunction
by
using
oxidative
phosphorylation
inhibitors
like
Lonidamine
(LND)
serve
multi‐immune
pathway
regulation
strategy
through
PD‐L1,
collagen,
TGF‐β
co‐depression.
Then,
IR‐LND
prepared
combining
mitochondria‐targeted
molecule
IR‐68
with
LND,
which
then
loaded
liposomes
(Lip)
create
IR‐LND@Lip
nanoadjuvants.
By
doing
this,
more
effectively
sensitizes
generating
cold
tumors
into
hot
ones
activation
co‐inhibition.
conclusion,
combined
treatment
ultimately
almost
completely
suppressed
bladder
breast
Cancer Drug Resistance,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 7, 2025
Cancer-associated
fibroblasts
(CAFs)
constitute
a
critical
component
of
the
tumor
microenvironment
(TME).
CAFs
can
be
reprogrammed
by
cancer
cells,
leading
to
production
extracellular
vesicles
(EVs).
These
EVs
serve
as
carriers
for
bioactive
substances,
including
proteins,
nucleic
acids,
and
metabolic
products,
thereby
facilitating
progression.
CAF-derived
exert
substantial
influence
on
cell
proliferation,
invasion,
metastasis,
immunological
environment,
processes
lymphangiogenesis
angiogenesis.
Despite
their
potential
non-invasive
biomarkers
therapeutic
delivery
vehicles,
clinical
application
is
currently
limited
challenges
in
purification
precise
targeting.
This
review
delineates
diverse
roles
growth,
immune
evasion
within
TME.
