From PD-1/PD-L1 to tertiary lymphoid structures: Paving the way for precision immunotherapy in cholangiocarcinoma treatment
Human Vaccines & Immunotherapeutics,
Год журнала:
2025,
Номер
21(1)
Опубликована: Янв. 6, 2025
Cholangiocarcinoma
(CCA)
is
a
highly
malignant
hepatobiliary
tumor
characterized
by
limited
treatment
options
and
poor
prognosis.
The
recent
rise
of
immunotherapy
has
significantly
influenced
research
in
this
field.
This
study
presents
bibliometric
analysis
416
articles
retrieved
from
the
WOSCC,
Wan
fang
Data,
CNKI
VIP
databases,
spanning
contributions
32
countries,
589
institutions
3,200
authors.
identified
"PD-L1,"
"PD-1"
"pembrolizumab"
as
central
foci,
while
"immune
checkpoint
inhibitors,"
"tumor
immune
microenvironment,"
"tertiary
lymphoid
structures"
"durvalumab"
emerged
key
areas
interest.
These
findings
emphasize
pivotal
role
improving
survival
outcomes
for
CCA,
they
highlight
significance
tertiary
structures
within
microenvironment
promising
target
future
research.
offers
strategic
overview
evolving
landscape
CCA
immunotherapy,
providing
valuable
insights
to
guide
scientific
endeavors
domain.
Язык: Английский
A Novel 167‐Amino Acid Protein Encoded by CircPCSK6 Inhibits Intrahepatic Cholangiocarcinoma Progression via IKBα Ubiquitination
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 21, 2025
Abstract
Intrahepatic
cholangiocarcinoma
(ICC),
a
formidable
challenge
in
oncology,
demands
innovative
biomarkers
and
therapeutic
targets.
This
research
highlights
the
importance
of
circular
RNA
(circRNA)
circPCSK6
its
peptide
derivative
circPCSK6‐167aa
ICC.
CircPCSK6
is
significantly
downregulated
both
ICC
patients
mouse
primary
models,
lower
expression
linked
to
adverse
prognosis,
highlighting
pivotal
role
pathogenesis.
Functionally,
this
study
elucidates
regulatory
effect
on
IκBα
ubiquitination
within
NF‐κB
pathway,
which
mediated
by
competitive
binding
E3
ligase
RBBP6.
complex
interaction
leads
reduced
activation
thereby
curbing
tumor
cell
proliferation,
migration,
invasion,
stemness,
hepatic‐lung
metastasis
vivo.
groundbreaking
discovery
expands
understanding
circRNA‐driven
tumorigenesis
through
atypical
signaling
pathways.
Additionally,
investigation
identified
EIF4A3
as
detrimental
regulator
circPCSK6,
exacerbating
malignancy.
Importantly,
leveraging
patient‐derived
xenograft
(PDX),
organoids,
organoid‐derived
PDX
higher
levels
enhance
sensitivity
gemcitabine,
indicating
potential
improve
effectiveness
chemotherapy.
These
insights
emphasize
promise
targeting
circPCSK6‐167aa,
offering
vital
biological
clinical
directions
for
developing
cutting‐edge
approaches,
thus
revealing
strategies
targets
future
treatments.
Язык: Английский
Deep immune profiling of intrahepatic cholangiocarcinoma with CODEX multiplexed imaging
Hepatology Communications,
Год журнала:
2025,
Номер
9(3)
Опубликована: Фев. 19, 2025
Background:
Intrahepatic
cholangiocarcinoma
(iCCA)
may
be
genomically
subclassified
by
the
presence
of
potentially
actionable
molecular
aberrations,
which
pathogenic
alterations
in
isocitrate
dehydrogenase
(IDH)1
and
fibroblast
growth
factor
receptor
(FGFR)2
are
most
frequently
observed.
The
impact
these
on
tumor
immune
microenvironment
remains
incompletely
understood.
Methods:
We
performed
a
high-parameter
spatial
phenotyping
iCCA
samples
with
FGFR2
or
IDH1
FGFR2/IDH1
wild-type
controls
at
single-cell
level
using
CO-Detection
indEXing.
Results:
A
total
24
tumors
were
examined.
Tumors
characterized
fewer
CD8+
T
cells
“M2-like”
macrophages
but
higher
levels
polymorphonuclear
myeloid-derived
suppressor
as
compared
to
tumors.
Spatial
relationships
between
multiple
other
cell
types
(including
cells,
CD4+,
cells)
enriched
alterations.
mutations
had
trend
toward
more
fibroblasts
closer
proximity
CD4+
structural
components
subtypes.
Conclusions:
iCCAs
fusions/rearrangements
have
distinct
immunophenotypes.
Tailoring
immunotherapeutic
approaches
specific
subsets
could
improve
treatment
outcomes
across
divergent
molecularly
defined
Язык: Английский
Frequent EPHA2 receptor mutations in cholangiocarcinoma disrupt receptor forward signaling supporting a tumor suppressor role
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 28, 2025
ABSTRACT
EPHA2
is
a
receptor
tyrosine
kinase
highly
expressed
in
many
cancers.
By
analyzing
cancer
patient
databases
for
mutations
the
coding
sequence,
we
found
that
cholangiocarcinoma
(a
hepatobiliary
with
dismal
prognosis)
exhibits
uniquely
high
incidence
of
mutations.
To
deUine
functional
signiUicance
these
mutations,
generated
representative
mutants
and
monitored
major
autophosphorylation
sites
as
indicative
activity-dependent
signal
transduction
(known
forward
signaling).
We
missense
ligand-binding
domain
abrogate
ligand
binding
ligand-induced
phosphorylation,
while
most
activity.
detected
less
pronounced
effects
other
domains,
which
vary
depending
on
phosphosite,
suggesting
might
differentially
affect
(or
bias)
different
downstream
signaling
pathways.
Other
introduce
early
stop
codons
encode
truncated
forms
lacking
all
or
part
domain.
also
an
secreted
form,
transmembrane
full-length
inactive
mutant
can
inhibit
phosphorylation
co-expressed
wild-type.
Taken
together,
data
suggest
interfering
facilitate
development.
indeed
obtained
evidence
mutant,
but
not
wild-type,
induce
proliferative
masses
consistent
well
differentiated
validated
mouse
model
cholangiocarcinogenesis.
our
Uindings
driver
gene
its
has
tumor
suppressor
Язык: Английский
Hepatic arterial infusion of GEMOX plus systemic gemcitabine chemotherapy combined with lenvatinib and PD-1 inhibitor in large unresectable intrahepatic cholangiocarcinoma
International Immunopharmacology,
Год журнала:
2024,
Номер
140, С. 112872 - 112872
Опубликована: Авг. 8, 2024
Язык: Английский
New Relevant Evidence in Cholangiocarcinoma Biology and Characterization
Cancers,
Год журнала:
2024,
Номер
16(24), С. 4239 - 4239
Опубликована: Дек. 19, 2024
Among
solid
tumors,
cholangiocarcinoma
(CCA)
emerges
as
one
of
the
most
difficult
to
eradicate.
The
silent
and
asymptomatic
nature
this
tumor,
particularly
in
its
early
stages,
well
high
heterogeneity
at
genomic,
epigenetic,
molecular
levels
delay
diagnosis,
significantly
compromising
efficacy
current
therapeutic
options
thus
contributing
a
dismal
prognosis.
Extensive
research
has
been
conducted
on
pathobiology
CCA,
recent
advances
have
made
classification
characterization
new
targets.
Both
targeted
therapy
immunotherapy
emerged
effective
safe
strategies
for
various
types
cancers,
demonstrating
potential
benefits
advanced
CCA.
Furthermore,
deeper
comprehension
cellular
components
tumor
microenvironment
(TME)
opened
up
possibilities
innovative
treatment
methods.
This
review
discusses
evidence
biology
highlighting
novel
possible
druggable
Язык: Английский