Upsala Journal of Medical Sciences,
Journal Year:
2024,
Volume and Issue:
129, P. e10710 - e10710
Published: May 24, 2024
Cancer-associated
fibroblasts
(CAFs)
are
a
heterogeneous
cell
population
recognized
as
key
component
of
the
tumour
microenvironment
(TME).
known
to
play
an
important
role
in
maintaining
and
remodelling
extracellular
matrix
(ECM)
stroma,
supporting
cancer
progression
inhibiting
immune
system’s
response
against
cells.
This
review
aims
summarize
immunomodulatory
roles
CAFs,
particularly
focussing
on
their
T-cell
suppressive
effects.
have
several
ways
by
which
they
can
affect
tumour’s
(TIME).
For
example,
interactions
with
macrophages
dendritic
cells
(DCs)
create
immunosuppressive
milieu
that
indirectly
anticancer
immunity
enable
evasion.
In
addition,
number
recent
studies
confirmed
CAF-mediated
direct
effects
capacity
through
ECM
remodelling,
promoting
expression
checkpoints,
cytokine
secretion
release
vesicles.
The
consequential
impact
CAFs
function
is
then
reflected
affecting
proliferation
apoptosis,
migration
infiltration,
differentiation
exhaustion.
Emerging
evidence
highlights
existence
specific
CAF
subsets
distinct
capabilities
modulate
landscape
TME
various
cancers,
suggesting
possibility
exploitation
possible
prognostic
biomarkers
therapeutic
targets.
Cancer Discovery,
Journal Year:
2024,
Volume and Issue:
14(6), P. 1018 - 1047
Published: April 6, 2024
Abstract
Understanding
the
role
of
tumor
microenvironment
(TME)
in
lung
cancer
is
critical
to
improving
patient
outcomes.
We
identified
four
histology-independent
archetype
TMEs
treatment-naïve
early-stage
using
imaging
mass
cytometry
TRACERx
study
(n
=
81
patients/198
samples/2.3
million
cells).
In
immune-hot
adenocarcinomas,
spatial
niches
T
cells
and
macrophages
increased
with
clonal
neoantigen
burden,
whereas
such
an
increase
was
observed
for
plasma
B
immune-excluded
squamous
cell
carcinomas
(LUSC).
Immune-low
were
associated
fibroblast
barriers
immune
infiltration.
The
fourth
archetype,
characterized
by
sparse
lymphocytes
high
tumor-associated
neutrophil
(TAN)
infiltration,
had
spatially
separated
from
vasculature
exhibited
low
intratumor
heterogeneity.
TAN-high
LUSC
frequent
PIK3CA
mutations.
tumors
harbored
recently
expanded
metastasis-seeding
subclones
a
shorter
disease-free
survival
independent
stage.
These
findings
delineate
genomic,
immune,
physical
surveillance
implicate
neutrophil-rich
metastasis.
Significance:
This
provides
novel
insights
into
organization
TME
context
immunogenicity,
heterogeneity,
evolution.
Pairing
evolutionary
history
resolved
suggests
mechanistic
hypotheses
progression
metastasis
implications
outcome
treatment.
article
featured
Selected
Articles
Issue,
p.
897
British Journal of Cancer,
Journal Year:
2024,
Volume and Issue:
130(11), P. 1758 - 1769
Published: April 6, 2024
Abstract
Background
Cancer-associated
fibroblasts
(CAFs)
are
a
dominant
cell
type
in
the
stroma
of
non-small
lung
cancer
(NSCLC).
Fibroblast
heterogeneity
reflects
subpopulations
CAFs,
which
can
influence
prognosis
and
treatment
efficacy.
We
describe
subtypes
CAFs
NSCLC.
Methods
Primary
human
NSCLC
resections
were
assessed
by
flow
cytometry
multiplex
immunofluorescence
for
markers
fibroblast
activation
allowed
identification
CAF
subsets.
Survival
data
analysed
our
cohort
consisting
163
patients
to
understand
prognostic
significance
Results
identified
five
populations,
termed
S1-S5.
CAF-S5
represents
previously
undescribed
population,
express
FAP
PDPN
but
lack
myofibroblast
marker
αSMA,
whereas
CAF-S1
populations
all
three.
spatially
further
from
tumour
regions
then
scRNA
demonstrate
an
inflammatory
phenotype.
The
presence
or
is
correlated
worse
survival
outcome
NSCLC,
despite
curative
resection,
highlighting
importance
TCGA
suggest
predominance
has
poor
across
several
types.
Conclusion
This
study
describes
novel
subset
where
its
correlates
outcome.
Cell Reports Medicine,
Journal Year:
2025,
Volume and Issue:
unknown, P. 101934 - 101934
Published: Feb. 1, 2025
Highlights•mTLSs
are
predictive
of
response
to
ICIs
in
NSCLC•Two
CAF
subsets
within
the
TME
key
determinants
primary
resistance
ICIs•FAP+αSMA+
CAFs
correlate
with
inflammatory
and
exhaustion
CD8+
T
cells•MYH11+αSMA+
favor
an
immunosuppressive
CD4+
Treg
cell
infiltrationSummaryEffectiveness
immune
checkpoint
inhibitors
(ICIs)
non-small
lung
cancer
(NSCLC)
has
been
linked
presence
mature
tertiary
lymphoid
structures
(mTLSs)
tumor
microenvironment
(TME).
However,
only
a
subset
mTLS-positive
NSCLC
derives
benefit,
thus
highlighting
need
unravel
ICI
determinants.
The
comprehensive
analysis
ICI-treated
patients
(n
=
509)
from
Bergonié
Institute
Profiling
(BIP)
study
(NCT02534649)
reveals
that
mTLSs
correlates
improved
clinical
outcomes,
independently
programmed
death
ligand
1
(PD-L1)
expression
genomic
features.
Employing
spatial
transcriptomics
alongside
multiplex
immunofluorescence
(mIF),
we
show
two
distinct
cancer-associated
fibroblasts
(CAFs)
essential
factors
mediating
NSCLC.
These
associated
exclusion,
exhaustion,
increased
regulatory
infiltration,
underscoring
TME.
Our
highlights
pivotal
role
specific
thwarting
ICIs,
proposing
new
therapeutic
targets
enhance
immunotherapy
efficacy.Graphical
abstract
Cell Communication and Signaling,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: Jan. 13, 2025
Ewing's
sarcoma
(EwS),
a
common
pediatric
bone
cancer,
is
associated
with
poor
survival
due
to
lack
of
therapeutic
targets
for
immunotherapy
or
targeted
therapy.
Therefore,
more
effective
treatment
options
are
urgently
needed.
Since
novel
immunotherapies
may
address
this
need,
we
performed
an
integrative
analysis
involving
single-cell
RNA
sequencing,
cell
function
experiments,
and
humanized
models
dissect
the
immunoregulatory
interactions
in
EwS
identify
strategies
optimizing
immunotherapeutic
efficacy.
infiltrated
by
immunosuppressive
myeloid
populations,
T
B
lymphocytes,
natural
killer
cells.
We
found
that
SLC40A1
C1QA
macrophages
were
prognosis,
whereas
CD8+
T-cell
infiltration
was
good
prognosis.
A
comparative
paired
samples
revealed
tumors
chemotherapeutic
response,
presented
increased
antigen
presentation
reduced
release
protumor
cytokines,
cells
cytotoxicity
exhaustion.
An
interaction
vast
network
identified
MIF-CD74
as
crucial
target
can
simultaneously
promote
M2
polarization
inhibit
infiltration.
Importantly,
MIF
blockade
effectively
reshaped
tumor
immune
microenvironment,
turning
cold
hot
inhibiting
growth.
Our
MIF/CD74
axis
promising
Ewing
provides
rationale
immunotherapy.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2025,
Volume and Issue:
44(1)
Published: Feb. 20, 2025
The
ubiquitously
expressed
transmembrane
protein,
Herpesvirus
Entry
Mediator
(HVEM),
functions
as
a
molecular
switch,
capable
of
both
activating
and
inhibiting
the
immune
response
depending
on
its
interacting
ligands.
HVEM-Fc
is
novel
recombinant
fusion
protein
with
potential
to
eradicate
tumor
cells.
anti-tumor
efficacy
was
evaluated
in
C57BL/6
mice-bearing
lung
cancer
models:
syngeneic
model
an
orthotopic
mouse
cancer.
Additionally,
patient-derived
organoids
were
employed
conjunction
T
cell
co-culture
systems.
To
investigate
underlying
mechanisms,
comprehensive
array
techniques
utilized,
including
single-cell
RNA
sequencing,
spatial
transcriptomics,
bulk
flow
cytometry.
Furthermore,
effects
combination
Programmed
Death-1
(PD-1)
inhibitors
assessed.
Finally,
depletion
antibodies
used
elucidate
mechanisms
action.
In
vivo,
1
mg/kg
demonstrated
effective
inhibition
growth
metastasis
mice
bearing
KP
Multi-omics
analysis
showed
that
induced
immune-stimulatory
microenvironment.
Notably,
PD-1
inhibitor
most
potent
growth.
vitro,
validated
cells
through
activation
non-small
(NSCLC)
models.
Our
data
demonstrate
exerts
strong
signal
augments
prolongs
T-cell
activity
murine
models
human
NSCLC
organoid
Moreover,
yields
outcomes.
Oncogene,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 26, 2025
Acquired
resistance
to
epidermal
growth
factor
receptor
tyrosine
kinase
inhibitors
(EGFR-TKIs)
remains
a
major
challenge
in
the
treatment
of
lung
cancer.
Cancer
associated
fibroblasts
(CAFs)
play
key
role
promoting
anti-cancer
therapies.
This
study
identified
subpopulation
CAFs
characterized
by
overexpression
collagen
triple
helix
repeat-containing
1
(CTHRC1)
through
single-cell
RNA
sequencing
cancer
patients
undergoing
EGFR-TKI
treatment.
These
CTHRC1+
were
enriched
drug-resistant
tumors.
Mechanistically,
enhance
glycolytic
activity
cells
activating
TGF-β/Smad3
signaling
pathway.
Excess
lactate
produced
process
glycolysis
further
upregulates
CTHRC1
expression
histone
lactylation,
creating
positive
feedback
loop
that
sustains
resistance.
The
also
demonstrated
Gambogenic
Acid,
natural
compound,
can
disrupt
this
loop,
thereby
improving
efficacy
therapy.
Additionally,
presence
tumor
tissues
could
serve
as
biomarker
for
predicting
response
therapy
and
patient
prognosis.
Overall,
highlights
significant
suggests
targeting
be
promising
strategy
overcome
drug