Anti-TGF-β/PD-L1 bispecific antibody synergizes with radiotherapy to enhance antitumor immunity and mitigate radiation-induced pulmonary fibrosis
Journal of Hematology & Oncology,
Год журнала:
2025,
Номер
18(1)
Опубликована: Март 5, 2025
Despite
the
success
of
immune
checkpoint
inhibitors
(ICIs)
in
multiple
malignant
tumors,
a
significant
proportion
patients
remain
unresponsive
to
treatment.
Radiotherapy
(RT)
elicits
immunogenic
antitumor
responses
but
concurrently
activates
several
evasion
mechanisms.
Our
earlier
research
demonstrated
efficacy
YM101,
an
anti-TGF-β/PD-L1
bispecific
antibody,
stroma-rich
tumors.
Nevertheless,
YM101
has
reduced
effectiveness
non-inflamed
tumors
characterized
by
poor
cell
infiltration.
This
study
investigated
potential
synergy
between
RT
and
overcoming
immunotherapy
resistance
mitigating
RT-induced
pulmonary
fibrosis.
The
activity
survival
outcomes
plus
treatment
vivo
were
explored
murine
tumor
models.
Furthermore,
inhibition
metastases
was
assessed
metastasis
model.
impact
on
dendritic
(DC)
maturation
quantified
flow
cytometry,
whereas
cytokine
chemokine
secretions
measured
ELISA.
To
comprehensively
characterize
changes
microenvironment,
we
utilized
combination
methods,
including
IHC
staining,
multiplex
inmunofluorecence
RNA
sequencing.
Additionally,
evaluated
significantly
inhibited
growth,
prolonged
compared
with
monotherapies
promoted
DC
dose-dependent
manner
increased
proinflammatory
cytokines.
Mechanistically,
simultaneously
infiltration
activation
intratumoral
DCs
tumor-infiltrating
lymphocytes
reshaped
microenvironment
landscape.
Notably,
attenuated
both
peritumoral
fibrosis
findings
suggest
that
combined
enhances
immunity
overcomes
preclinical
models,
while
showing
therapy
demonstrates
promise
ICI
resistance,
potentially
sparing
normal
tissue,
thereby
providing
strong
rationale
for
further
clinical
investigations.
Язык: Английский
Mechanisms of radiation‐induced tissue damage and response
MedComm,
Год журнала:
2024,
Номер
5(10)
Опубликована: Сен. 20, 2024
Radiation-induced
tissue
injury
(RITI)
is
the
most
common
complication
in
clinical
tumor
radiotherapy.
Due
to
heterogeneity
response
of
different
tissues
radiation
(IR),
radiotherapy
will
cause
types
and
degrees
RITI,
which
greatly
limits
application
Efforts
are
continuously
ongoing
elucidate
molecular
mechanism
RITI
develop
corresponding
prevention
treatment
drugs
for
RITI.
Single-cell
sequencing
(Sc-seq)
has
emerged
as
a
powerful
tool
uncovering
mechanisms
identifying
potential
targets
by
enhancing
our
understanding
complex
intercellular
relationships,
facilitating
identification
novel
cell
phenotypes,
allowing
assessment
spatiotemporal
developmental
trajectories.
Based
on
comprehensive
review
we
analyzed
regulatory
networks
combination
with
Sc-seq
summarized
targeted
intervention
pathways
therapeutic
Deciphering
diverse
underlying
can
shed
light
its
pathogenesis
unveil
new
avenues
potentially
facilitate
repair
or
regeneration
currently
irreversible
Furthermore,
discuss
how
personalized
strategies
based
offer
promise
mitigating
Язык: Английский
Clinical development complexity of TGF-β inhibition: From fibrosis to cancer immunotherapy
International review of cell and molecular biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Язык: Английский
Diagnosis and treatment of radiation induced pneumonitis in patients with lung cancer: An ESTRO clinical practice guideline
Radiotherapy and Oncology,
Год журнала:
2025,
Номер
unknown, С. 110837 - 110837
Опубликована: Апрель 1, 2025
The
incidence
of
radiation
pneumonitis
(RP)
has
decreased
significantly
compared
to
historical
series,
mainly
due
improved
radiotherapy
techniques
and
patient
selection.
Nevertheless,
some
patients
still
develop
RP.
This
guideline
provides
user-friendly
flowcharts
address
common
clinical
practice
questions
regarding
We
summarize
the
current
state
art
mechanisms,
risk
factors,
diagnosis
treatment
Dosimetric
constraints
minimize
RP,
as
well
factors
for
developing
such
idiopathic
pulmonary
fibrosis
(IPF)
were
identified.
combination
medication
a
factor
development
RP
was
reviewed.
remains
exclusion,
but
an
algorithm
reaching
been
proposed.
Finally,
practical
approaches
are
outlined.
Язык: Английский
ITGAV, a specific biomarker associated with the pathogenesis of idiopathic pulmonary fibrosis
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Май 15, 2025
Objective
Idiopathic
pulmonary
fibrosis
(IPF),
which
radiologically/pathologically
manifests
mainly
as
usual
interstitial
pneumonia
(UIP),
is
easily
confused
with
chronic
hypersensitivity
pneumonitis
(CHP)
and
collagenous
vascular
disease
in
clinical
settings,
affecting
the
physician's
diagnosis
treatment.
Accurate
identification
of
IPF
from
various
diseases
presenting
UIP
essential
for
effective
therapy.
Methods
Gene
expression
data
CHP,
IPF,
rheumatoid
arthritis-UIP
samples
were
downloaded
GEO
database,
specific
biomarkers
identified
to
differentiate
idiopathic
UIP/IPF
secondary
UIP.
We
compared
gene
between
control,
UIP,
groups.
The
mechanism
PF
was
explored
by
immunohistochemistry,
quantitative
polymerase
chain
reaction,
immunofluorescence,
flow
cytometry.
Results
integrin
alpha
V
(ITGAV)
a
biomarker
distinguishing
observed
gradual
increase
ITGAV
across
Animal
studies
indicated
that
elevated
immune
cells,
particularly
monocyte-derived
macrophages,
contributed
development
PF.
Conclusion
linked
pathogenesis
IPF.
provides
new
perspectives
diagnosis,
mechanistic
drug
Язык: Английский
Therapieinduzierte Pneumonitis in der Thoraxonkologie
Deleted Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 27, 2025
Regulation of idiopathic pulmonary fibrosis: a cross-talk between TGF-β signaling and MicroRNAs
Frontiers in Medicine,
Год журнала:
2024,
Номер
11
Опубликована: Сен. 25, 2024
Pulmonary
fibrosis
(PF)
is
a
highly
complex
and
challenging
disease
affecting
the
respiratory
system.
Patients
with
PF
usually
have
an
abbreviated
survival
period
consequential
high
mortality
rate
after
diagnosis
confirmed,
posing
serious
threats
to
human
health.
In
clinical
practice,
typically
treated
by
antifibrotic
agents,
such
as
Pirfenidone
Nintedanib.
However,
these
agents
been
reported
correlate
substantial
adverse
effects,
escalating
costs,
insufficient
efficacy.
Moreover,
it
remains
unclarified
about
multifactorial
pathology
of
PF.
Therefore,
there
urgent
demand
for
elucidating
underlying
mechanisms
identifying
safe,
efficient,
targeted
therapeutic
strategies
treatment.
The
crucial
role
transforming
growth
factor-
β
(TGF-β)
signaling
pathway
in
development
has
explored
many
studies.
MicroRNAs
(miRNAs),
which
function
post-transcriptional
regulators
gene
expression,
can
significantly
affect
modulating
TGF-
signaling.
turn,
TGF-β
regulate
expression
biogenesis
miRNAs,
thereby
substantially
progression
Hence,
that
focus
on
drug-targeted
regulation
either
augmenting
down-regulated
miRNAs
or
inhibiting
overexpressed
may
hinder
pathways
related
These
contribute
prevention
suppression
provide
novel
insights
into
treatment
this
disease.
Язык: Английский
High-dose vitamin C attenuates radiation-induced pulmonary fibrosis by targeting S100A8 and S100A9
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease,
Год журнала:
2024,
Номер
1870(7), С. 167358 - 167358
Опубликована: Июль 18, 2024
Radiation-induced
pulmonary
fibrosis
(RIPF)
is
a
frequently
encountered
late
complication
in
patients
undergoing
radiation
therapy,
presenting
substantial
risk
to
patient
mortality
and
quality
of
life.
The
pathogenesis
RIPF
remains
unclear,
current
treatment
options
are
limited
efficacy.
High-dose
vitamin
C
has
demonstrated
potential
when
used
conjunction
with
other
adjuvant
therapies
due
potent
anticancer
properties.
However,
the
relationship
between
high-dose
not
yet
been
explored
existing
literature.
In
our
study,
model
LLC
tumor
were
as
two
animal
models
explore
how
can
improve
without
hampering
antitumour
efficacy
radiotherapy.
impact
on
was
assessed
through
various
assays,
including
micro-CT,
HE
staining,
Masson
immunohistochemistry.
Our
results
indicated
that
administering
2
days
before
continuing
for
duration
6
weeks
significantly
inhibited
progression
RIPF.
order
mechanism
by
which
attenuates
RIPF,
we
utilized
RNA-seq
analysis
mouse
lung
tissue
publicly
available
databases.
findings
inhibits
differentiation
fibroblasts
into
myofibroblasts
targeting
S100A8
S100A9
derived
from
neutrophils.
Additionally,
combination
enhanced
inhibition
growth
murine
model.
These
revealed
radiotherapy
may
offer
promising
therapeutic
approach
clinical
management
thoracic
tumors
prevention
Язык: Английский
Quantitative proteomics reveals the mechanism of endoplasmic reticulum stress-mediated pulmonary fibrosis in mice
Heliyon,
Год журнала:
2024,
Номер
10(20), С. e39150 - e39150
Опубликована: Окт. 1, 2024
Pulmonary
fibrosis
is
a
progressive
disease
that
can
lead
to
respiratory
failure.
Many
types
of
cells
are
involved
in
the
progression
pulmonary
fibrosis.
This
study
utilized
quantitative
proteomics
investigate
mechanism
TGF-β-induced
fibrosis-like
changes
mouse
epithelial
cells.
Our
findings
revealed
TGF-β
significantly
impacted
biological
processes
related
endoplasmic
reticulum,
mitochondrion,
and
ribonucleoprotein
complex.
Pull-down
assay
coupled
with
identified
114
proteins
may
directly
interact
TGF-β,
their
functions
were
mitochondria,
translation,
ubiquitin
ligase
conjugation,
mRNA
processing,
actin
binding.
Among
them,
17
molecules
also
found
different
expression
(DEPs)
proteomic,
such
as
H1F0,
MED21,
SDF2L1,
DAD1,
TMX1.
Additionally,
decreased
folded
structure
number
ribosomes
reticulum
increased
key
unfolded
protein
response,
including
HRD1,
PERK,
ERN1.
Overall,
our
suggested
induced
fibrotic
lung
by
ER
stress
initiated
response
through
PRKCSH/IRE1
PERK/GADD34/CHOP
signaling
pathways.
Язык: Английский