Molecular Cancer,
Journal Year:
2023,
Volume and Issue:
22(1)
Published: Oct. 13, 2023
Cancer-associated
fibroblasts
(CAFs)
are
a
heterogeneous
cell
population
that
plays
crucial
role
in
remodeling
the
tumor
microenvironment
(TME).
Here,
through
integrated
analysis
of
spatial
and
single-cell
transcriptomics
data
across
six
common
cancer
types,
we
identified
four
distinct
functional
subgroups
CAFs
described
their
distribution
characteristics.
Additionally,
RNA
sequencing
(scRNA-seq)
from
three
additional
types
two
newly
generated
scRNA-seq
datasets
rare
namely
epithelial-myoepithelial
carcinoma
(EMC)
mucoepidermoid
(MEC),
expanded
our
understanding
CAF
heterogeneity.
Cell-cell
interaction
conducted
within
context
highlighted
pivotal
roles
matrix
(mCAFs)
angiogenesis
inflammatory
(iCAFs)
shaping
immunosuppressive
microenvironment.
In
patients
with
breast
(BRCA)
undergoing
anti-PD-1
immunotherapy,
iCAFs
demonstrated
heightened
capacity
facilitating
proliferation,
promoting
epithelial-mesenchymal
transition
(EMT),
contributing
to
establishment
an
Furthermore,
scoring
system
based
on
showed
significant
correlation
immune
therapy
response
melanoma
patients.
Lastly,
provided
web
interface
(
https://chenxisd.shinyapps.io/pancaf/
)
for
research
community
investigate
pan-cancer.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: June 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.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: March 20, 2024
T
cell-based
immunotherapies
have
exhibited
promising
outcomes
in
tumor
control;
however,
their
efficacy
is
limited
immune-excluded
tumors.
Cancer-associated
fibroblasts
(CAFs)
play
a
pivotal
role
shaping
the
microenvironment
and
modulating
immune
infiltration.
Despite
identification
of
distinct
CAF
subtypes
using
single-cell
RNA-sequencing
(scRNA-seq),
functional
impact
on
hindering
T-cell
infiltration
remains
unclear,
particularly
soft-tissue
sarcomas
(STS)
characterized
by
low
response
rates
to
therapies.
In
this
study,
we
characterize
STS
murine
models
(in
female
mice)
with
composition
scRNA-seq,
identify
subset
CAFs
termed
glycolytic
cancer-associated
(glyCAF).
GlyCAF
rely
GLUT1-dependent
expression
CXCL16
impede
cytotoxic
into
parenchyma.
Targeting
glycolysis
decreases
restrictive
glyCAF
accumulation
at
margin,
thereby
enhancing
augmenting
chemotherapy.
These
findings
highlight
avenues
for
combinatorial
therapeutic
interventions
possibly
other
solid
Further
investigations
clinical
trials
are
needed
validate
these
potential
strategies
translate
them
practice.
Advanced Materials,
Journal Year:
2024,
Volume and Issue:
36(25)
Published: March 12, 2024
Abstract
The
dense
extracellular
matrix
(ECM)
in
solid
tumors,
contributed
by
cancer‐associated
fibroblasts
(CAFs),
hinders
penetration
of
drugs
and
diminishes
their
therapeutic
outcomes.
A
sequential
treatment
strategy
remodeling
the
ECM
via
a
CAF
modifier
(dasatinib,
DAS)
is
proposed
to
promote
an
immunogenic
cell
death
(ICD)
inducer
(epirubicin,
Epi)
apoptotic
vesicles,
ultimately
enhancing
efficacy
against
breast
cancer.
Dendritic
poly(oligo(ethylene
glycol)
methyl
ether
methacrylate)
(POEGMA)‐based
nanomedicines
(poly[OEGMA‐Dendron(G2)‐Gly‐Phe‐Leu‐Gly‐DAS]
(P‐DAS)
poly[OEGMA‐Dendron(G2)‐hydrazone‐Epi]
(P‐Epi))
are
developed
for
delivery
DAS
Epi,
respectively.
P‐DAS
reprograms
CAFs
reduce
collagen
downregulating
anabolism
energy
metabolism,
thereby
reducing
deposition.
regulated
can
enhance
tumor
P‐Epi
strengthen
its
ICD
effect,
leading
amplified
antitumor
immune
response.
In
cancer‐bearing
mice,
this
approach
alleviates
barrier,
resulting
reduced
burden
increased
cytotoxic
T
lymphocyte
infiltration,
more
encouragingly,
synergizes
effectively
with
anti‐programmed
1
(PD‐1)
therapy,
significantly
inhibiting
growth
preventing
lung
metastasis.
Furthermore,
systemic
toxicity
barely
detectable
after
P‐Epi.
This
opens
new
avenue
treating
desmoplastic
tumors
metabolically
targeting
overcome
barrier.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: April 27, 2024
Abstract
Pancreatic
ductal
adenocarcinoma
(PDAC)
is
a
highly
metastatic
disease
for
which
better
therapies
are
urgently
needed.
Fibroblasts
and
macrophages
heterogeneous
cell
populations
able
to
enhance
metastasis,
but
the
role
of
macrophage-fibroblast
crosstalk
in
regulating
their
pro-metastatic
functions
remains
poorly
understood.
Here
we
deconvolve
how
regulate
metastasis-associated
fibroblast
(MAF)
heterogeneity
liver.
We
identify
three
functionally
distinct
MAF
populations,
among
generation
immunoregulatory
myofibroblastic-MAFs
(myMAFs)
critically
depends
on
macrophages.
Mechanistically,
myMAFs
induced
through
STAT3-dependent
mechanism
driven
by
macrophage-derived
progranulin
cancer
cell-secreted
leukaemia
inhibitory
factor
(LIF).
In
reciprocal
manner,
myMAF
secreted
osteopontin
promotes
an
immunosuppressive
macrophage
phenotype
resulting
inhibition
cytotoxic
T
functions.
Pharmacological
blockade
STAT3
or
myMAF-specific
genetic
depletion
restores
anti-tumour
immune
response
reduces
metastases.
Our
findings
provide
molecular
insights
into
complex
macrophage–fibroblast
interactions
tumours
reveal
potential
targets
inhibit
PDAC
liver
metastasis.
Signal Transduction and Targeted Therapy,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: Feb. 11, 2025
Abstract
Accumulated
evidence
has
implicated
the
diverse
and
substantial
influence
of
lactate
on
cellular
differentiation
fate
regulation
in
physiological
pathological
settings,
particularly
intricate
conditions
such
as
cancer.
Specifically,
been
demonstrated
to
be
pivotal
molding
tumor
microenvironment
(TME)
through
its
effects
different
cell
populations.
Within
cells,
impacts
signaling
pathways,
augments
shuttle
process,
boosts
resistance
oxidative
stress,
contributes
lactylation.
In
various
populations,
interplay
between
immune
cells
governs
processes
differentiation,
response,
surveillance,
treatment
effectiveness.
Furthermore,
communication
stromal/endothelial
supports
basal
membrane
(BM)
remodeling,
epithelial-mesenchymal
transitions
(EMT),
metabolic
reprogramming,
angiogenesis,
drug
resistance.
Focusing
production
transport,
specifically
dehydrogenase
(LDH)
monocarboxylate
transporters
(MCT),
shown
promise
Inhibitors
targeting
LDH
MCT
act
both
suppressors
enhancers
immunotherapy,
leading
a
synergistic
therapeutic
effect
when
combined
with
immunotherapy.
The
review
underscores
importance
progression
provides
valuable
perspectives
potential
approaches
that
target
vulnerability
metabolism,
highlighting
Heel
Achilles
for
cancer
treatment.
