Seminars in Cancer Biology,
Journal Year:
2019,
Volume and Issue:
62, P. 166 - 181
Published: Aug. 12, 2019
The
tumor
microenvironment
(TME)
is
a
complex
meshwork
of
extracellular
matrix
(ECM)
macromolecules
filled
with
collection
cells
including
cancer-associated
fibroblasts
(CAFs),
blood
vessel
associated
smooth
muscle
cells,
pericytes,
endothelial
mesenchymal
stem
and
variety
immune
cells.
In
tumors
the
homeostasis
governing
ECM
synthesis
turnover
disturbed
resulting
in
abnormal
formation
excessive
fibrillar
collagen
accumulations
varying
stiffness
organization.
opens
up
for
new
types
paracrine,
cell-cell
cell-ECM
interactions
large
consequences
growth,
angiogenesis,
metastasis,
suppression
resistance
to
treatments.
As
main
producer
paracrine
signals
CAF
central
cell
type
these
events.
Whereas
signaling
has
been
extensively
studied
context
tumor-stroma
interactions,
nature
numerous
integrin-mediated
occurring
TME
remains
understudied.
this
review
we
will
discuss
dissect
role
known
potential
TME,
during
both
tumorigenesis
chemoresistance-induced
events,
special
focus
on
"interaction
landscape"
desmoplastic
breast,
lung
pancreatic
cancers.
an
example
multifaceted
mode
action
stromal
receptor
integrin
α11β1,
summarize
our
current
understanding
CAF-expressed
three
types.
Molecular Cancer,
Journal Year:
2019,
Volume and Issue:
18(1)
Published: March 30, 2019
In
the
last
decades,
role
of
microenvironment
in
tumor
progression
and
therapeutic
outcome
has
gained
increasing
attention.
Cancer-associated
fibroblasts
(CAFs)
have
emerged
as
key
players
among
stromal
cells,
owing
to
their
abundance
most
solid
tumors
diverse
tumor-restraining/promoting
roles.
The
interplay
between
cells
neighboring
CAFs
takes
place
by
both
paracrine
signals
(cytokines,
exosomes
metabolites)
or
multifaceted
functions
surrounding
extracellular
matrix.
Here,
we
dissect
recent
identified
mechanisms
underlying
CAF-mediated
control
therapy
resistance,
which
include
induction
epithelial-to-mesenchymal
transition
(EMT),
activation
survival
pathways
stemness-related
programs
metabolic
reprogramming
cells.
Importantly,
recently
unveiled
heterogeneity
claims
tailored
efforts
aimed
at
eradicating
specific
subset
facilitating
progression,
resistance
relapse.
However,
despite
large
amount
pre-clinical
data,
much
effort
is
still
needed
translate
CAF-directed
anti-cancer
strategies
from
bench
clinic.
Signal Transduction and Targeted Therapy,
Journal Year:
2021,
Volume and Issue:
6(1)
Published: June 10, 2021
Abstract
To
flourish,
cancers
greatly
depend
on
their
surrounding
tumor
microenvironment
(TME),
and
cancer-associated
fibroblasts
(CAFs)
in
TME
are
critical
for
cancer
occurrence
progression
because
of
versatile
roles
extracellular
matrix
remodeling,
maintenance
stemness,
blood
vessel
formation,
modulation
metabolism,
immune
response,
promotion
cell
proliferation,
migration,
invasion,
therapeutic
resistance.
CAFs
highly
heterogeneous
stromal
cells
crosstalk
with
is
mediated
by
a
complex
intricate
signaling
network
consisting
transforming
growth
factor-beta,
phosphoinositide
3-kinase/AKT/mammalian
target
rapamycin,
mitogen-activated
protein
kinase,
Wnt,
Janus
kinase/signal
transducers
activators
transcription,
epidermal
factor
receptor,
Hippo,
nuclear
kappa-light-chain-enhancer
activated
B
cells,
etc.,
pathways.
These
signals
exhibit
own
special
characteristics
during
the
have
potential
to
be
targeted
anticancer
therapy.
Therefore,
comprehensive
understanding
these
cascades
interactions
between
necessary
fully
realize
pivotal
cancers.
Herein,
this
review,
we
will
summarize
enormous
amounts
findings
mediating
its
related
targets
or
trials.
Further,
hypothesize
three
targeting
strategies,
including,
namely,
epithelial–mesenchymal
common
targets,
sequential
perturbation,
crosstalk-directed
paving
way
CAF-directed
host
cell-directed
antitumor
Cell Death and Disease,
Journal Year:
2019,
Volume and Issue:
10(8)
Published: July 15, 2019
Abstract
Head
and
neck
squamous
cell
carcinomas
(HNSCCs)
are
an
aggressive,
genetically
complex
difficult
to
treat
group
of
cancers.
In
lieu
truly
effective
targeted
therapies,
surgery
radiotherapy
represent
the
primary
treatment
options
for
most
patients.
But
these
treatments
associated
with
significant
morbidity
a
reduction
in
quality
life.
Resistance
both
only
available
therapy,
subsequent
relapse
common.
Research
has
therefore
focussed
on
identifying
biomarkers
stratify
patients
into
clinically
meaningful
groups
develop
more
therapies.
However,
as
we
now
discovering,
poor
response
therapy
aggressive
nature
HNSCCs
is
not
affected
by
alterations
intracellular
signalling
pathways
but
also
heavily
influenced
behaviour
extracellular
microenvironment.
The
HNSCC
tumour
landscape
environment
permissive
tumours’
nature,
fostered
actions
immune
system,
hypoxia
influence
microbiome.
Solving
challenges
rests
expanding
our
knowledge
areas,
parallel
greater
understanding
molecular
biology
subtypes.
This
update
aims
build
earlier
2014
review
bringing
up
date
provide
insights
areas
ongoing
research
perspectives
future.
Cancer Cell,
Journal Year:
2022,
Volume and Issue:
40(6), P. 656 - 673.e7
Published: May 5, 2022
Recent
studies
have
identified
a
unique
cancer-associated
fibroblast
(CAF)
population
termed
antigen-presenting
CAFs
(apCAFs),
characterized
by
the
expression
of
major
histocompatibility
complex
class
II
molecules,
suggesting
function
in
regulating
tumor
immunity.
Here,
integrating
multiple
single-cell
RNA-sequencing
and
performing
robust
lineage-tracing
assays,
we
find
that
apCAFs
are
derived
from
mesothelial
cells.
During
pancreatic
cancer
progression,
cells
form
downregulating
features
gaining
fibroblastic
features,
process
induced
interleukin-1
transforming
growth
factor
β.
directly
ligate
induce
naive
CD4+
T
into
regulatory
(Tregs)
an
antigen-specific
manner.
Moreover,
treatment
with
antibody
targeting
cell
marker
mesothelin
can
effectively
inhibit
to
apCAF
transition
Treg
formation
apCAFs.
Taken
together,
our
study
elucidates
how
may
contribute
immune
evasion
provides
insight
on
strategies
enhance
therapy.
Signal Transduction and Targeted Therapy,
Journal Year:
2020,
Volume and Issue:
5(1)
Published: Oct. 19, 2020
Abstract
Metabolic
reprogramming
is
reported
to
be
one
of
the
hallmarks
cancer,
which
an
adaptive
mechanism
by
fast-growing
cancer
cells
adapt
their
increasing
energy
demands.
Recently,
extracellular
vesicles
(EVs)
known
as
exosomes
have
been
recognized
crucial
signaling
mediators
in
regulating
tumor
microenvironment
(TME).
Meanwhile,
TME
a
highly
heterogeneous
ecosystem
incorporating
cells,
fibroblasts,
adipocytes,
endothelial
mesenchymal
stem
and
matrix.
Accumulated
evidence
indicates
that
may
transfer
biologically
functional
molecules
recipient
facilitate
progression,
angiogenesis,
metastasis,
drug
resistance,
immunosuppression
metabolism
surrounding
stromal
cells.
In
this
review,
we
present
role
underlying
how
exacerbate
development
through
metabolic
reprogramming.
addition,
will
also
discuss
potential
targeting
process
biomarkers
for
diagnosis
prognosis,
exosomes-mediated
targets
therapy.
Furthermore,
better
understanding
link
between
reprogramming,
impact
on
would
provide
novel
insights
prevention
treatment
future.
Frontiers in Immunology,
Journal Year:
2019,
Volume and Issue:
10
Published: July 19, 2019
In
cancer,
T
cells
become
dysfunctional
owing
to
persistent
antigen
exposure.
Dysfunctional
are
characterized
by
reduced
proliferative
capacity,
decreased
effector
function,
and
overexpression
of
multiple
inhibitory
receptors.
Due
the
presence
various
signals
in
complex
tumor
microenvironment,
tumor-specific
have
distinct
dysfunction
states.
Therapeutic
reactivation
has
yielded
good
results
cancer
patients.
Here,
we
review
hallmarks
cell
cancer.
Also,
discuss
relationship
between
immunotherapy.
