Cancer Letters,
Journal Year:
2023,
Volume and Issue:
578, P. 216463 - 216463
Published: Oct. 20, 2023
The
role
of
long
non-coding
RNA
(lncRNA)
in
the
progression
renal
cell
carcinoma
(RCC)
remains
further
study.
Whether
lncRNA
may
be
used
to
predict
immunotherapy
efficacy
RCC
is
less
studied.
In
this
study,
LINC00926
was
found
mainly
located
cytoplasm
by
FISH
and
nuclear-cytoplasmic
fractionation.
Downregulation
lines
inhibited
metastasis
cells.
pull-down
assay
dual-luciferase
reporter
demonstrated
that
functioned
as
miR-30a-5p
sponge
facilitate
SOX4
expression.
overexpression
BALB/c
mice
enhanced
PD-L1
surface
expression
resulted
immune
escape.
Mechanistic
investigations
showed
competitively
bound
Lyn,
leading
inhibition
CBL-mediated
ubiquitination
degradation,
stabilized
contributing
activation
IFNγ-JAK2-STAT1
signaling
pathway.
Moreover,
LINC00926,
together
with
or
PD-1
expression,
overall
survival
patients.
Therefore,
has
potential
a
novel
therapeutic
target
biomarker
ICB
response
RCC.
Molecular Cancer,
Journal Year:
2024,
Volume and Issue:
23(1)
Published: Sept. 2, 2024
Programmed
death
receptor-1
(PD-1)
and
its
ligand,
programmed
ligand-1
(PD-L1)
are
essential
molecules
that
key
in
modulating
immune
responses.
PD-L1
is
constitutively
expressed
on
various
cells,
epithelial
cancer
where
it
functions
as
a
co-stimulatory
molecule
capable
of
impairing
T-cell
mediated
Upon
binding
to
PD-1
activated
T-cells,
the
PD-1/PD-L1
interaction
triggers
signaling
pathways
can
induce
apoptosis
or
anergy,
thereby
facilitating
escape
tumors.
In
urological
cancers,
including
bladder
(BCa),
renal
cell
carcinoma
(RCC),
prostate
(PCa),
upregulation
has
been
demonstrated.
It
linked
poor
prognosis
enhanced
tumor
evasion.
Recent
studies
have
highlighted
significant
role
axis
mechanisms
cancers.
The
between
T-cells
further
contributes
immunosuppression
by
inhibiting
activation
proliferation.
Clinical
applications
checkpoint
inhibitors
shown
promising
efficacy
treating
advanced
significantly
improving
patient
outcomes.
However,
resistance
these
therapies,
either
intrinsic
acquired,
remains
challenge.
This
review
aims
provide
comprehensive
overview
pathway
We
summarize
regulatory
mechanism
underlying
expression
activity,
genetic,
epigenetic,
post-transcriptional,
post-translational
modifications.
Additionally,
we
discuss
current
clinical
research
inhibitors,
their
therapeutic
potential,
challenges
associated
with
resistance.
Understanding
crucial
for
developing
new
strategies
overcome
limitations
enhance
immunotherapy.
Cell Death and Disease,
Journal Year:
2024,
Volume and Issue:
15(8)
Published: Aug. 1, 2024
Abstract
Resistance
to
epidermal
growth
factor
receptor
(EGFR)–tyrosine
kinase
inhibitors
(TKIs)
is
a
significant
cause
of
treatment
failure
and
cancer
recurrence
in
non-small
cell
lung
(NSCLC).
Approximately
30%
patients
with
EGFR-activating
mutations
exhibit
primary
resistance
EGFR–TKIs.
However,
the
potential
mechanisms
EGFR–TKIs
remain
poorly
understood.
Recent
studies
have
shown
that
increased
expression
programmed
death
ligand-1
(PD-L1)
associated
resistance.
Therefore,
present
study
aimed
investigate
mechanism
PD-L1
EGFR-mutant
adenocarcinoma
(LUAD)
cells.
We
found
was
poor
prognosis
LUAD,
while
combination
chemotherapy
could
improve
its
therapeutic
efficacy.
In
vitro
vivo
experiments
revealed
promoted
proliferation
autophagy
inhibited
apoptosis
LUAD
Mechanistic
demonstrated
upregulation
critical
inducing
through
mitogen-activated
protein
(MAPK)
signaling
pathway,
which
beneficial
for
tumor
progression
development
gefitinib
Furthermore,
we
combined
pemetrexed
synergistically
enhance
antitumor
efficacy
PD-L1-overexpression
Overall,
our
contributed
cells,
may
be
mediated
by
via
MAPK
pathway.
These
findings
not
only
help
but
also
provide
reference
research
other
types.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(8), P. 6027 - 6043
Published: April 10, 2024
Targeting
the
programmed
cell
death
protein-1
(PD-1)/programmed
death-ligand
1
(PD-L1)
pathway
has
evolved
into
one
of
most
promising
strategies
for
tumor
immunotherapy.
Thus
far,
multiple
monoclonal
antibody
drugs
have
been
approved
treating
a
variety
tumors,
while
development
small-molecule
PD-1/PD-L1
inhibitors
lagged
far
behind,
with
only
few
entering
clinical
trials.
In
addition
to
and
inhibitors,
reducing
expression
levels
PD-L1
attracted
extensive
research
interest
as
another
strategy
target
pathway.
Herein,
we
analyze
structures
mechanisms
molecules
that
reduce
classify
them
degraders
downregulators
according
whether
they
directly
bind
PD-L1.
Moreover,
discuss
potential
prospects
developing
PD-L1-targeting
based
on
these
molecules.
It
is
hoped
this
perspective
will
provide
profound
insights
discovery
potent
antitumor
immunity
drugs.
Cancer Letters,
Journal Year:
2024,
Volume and Issue:
586, P. 216675 - 216675
Published: Jan. 25, 2024
Gallbladder
cancer
(GBC)
is
among
the
most
common
malignancies
of
biliary
tract
system
due
to
its
limited
treatments.
The
immunotherapeutic
targets
for
T
cells
are
appealing,
however,
heterogeneity
hinds
further
development.
We
systematically
construct
cell
atlas
by
single-cell
RNA
sequencing;
and
utilized
identified
gene
signatures
high_CNV_T
predict
molecular
subtyping
towards
personalized
therapeutic
treatments
GBC.
12
subtypes,
where
exhausted
CD8+
cells,
activated/exhausted
regulatory
were
predominant
in
tumors.
There
appeared
be
an
inverse
relationship
between
Th17
Treg
populations
with
levels
significantly
reduced,
whereas
Tregs
concomitantly
increased.
Furthermore,
we
first
established
criterion
identify
three
subtypes
GBC
based
on
their
pro-tumorigenic
microenvironments,
e.g.,
type
1
group
shows
more
M2
macrophages
infiltration,
while
2
infiltrated
highly
B
suppressive
activities.
Our
study
provides
valuable
insights
into
suggests
that
might
provide
a
potential
strategy
improve
treatment.
