bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Окт. 27, 2023
ABSTRACT
BACKGROUND
Non-muscle-invasive
bladder
cancer
(NMIBC)
poses
clinical
challenges
due
to
its
high
recurrence
and
progression
rates.
While
Bacillus
Calmette-Guérin
(BCG)
remains
as
the
gold
standard
treatment
for
high-risk
NMIBC,
recent
irruption
of
anti-PD-1/PD-L1
drugs
claims
a
comprehensive
understanding
tumour
microenvironment
(TME)
these
tumors.
METHODS
The
present
prospective
study
consisted
on
analysis
98
fresh
NMIBC
samples,
tumor
non-pathological
tissue,
via
flow
cytometry.
Final
included
distribution
11
cell
types
expression
PD-L1
in
66
62
tissue
biopsies
from
73
patients
(84.4%
paired
samples).
results
were
validated
using
publicly
available
transcriptomic
data,
histology.
RESULTS
In
comparison
TME
presented
microvascular
alterations,
increased
cancer-associated
fibroblast
(CAF)
myofibroblast
(myoCAF)
presence,
varied
immune
distribution.
Heterogeneous
was
observed
across
subsets,
with
cells
primary
potential
anti-PD-L1
binding
targets.
Unbiased
revealed
that
myoCAF
M2-like
macrophages
are
enriched
grade
tumors,
but
only
associated
higher
rates
recurrence,
we
confirmed
three
independent
cohorts
(888
total
patients).
We
further
prognostic
value
myoCAFs
by
micro-array.
CONCLUSION
This
provides
roadmap
establish
full
landscape
NMIBĆs
TME,
highlighting
markers.
FUNDING
funded
FC
AECC
(INVES222946GARC),
Consejería
de
Educación,
Ciencia
y
Universidades
la
CAM
(2018-T2/BMD-10342),
Hoffmann-La
Roche,
Ministerio
e
Innovación
(INMUNOEPIBLA)
ISCIII/FEDER
(CIBERONC
CB16/12/00489)
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Апрель 26, 2023
Immunotherapy
has
revolutionized
cancer
treatment
and
revitalized
efforts
to
harness
the
power
of
immune
system
combat
a
variety
types
more
effectively.
However,
low
clinical
response
rates
differences
in
outcomes
due
variations
landscape
among
patients
with
continue
be
major
limitations
immunotherapy.
Recent
improve
responses
immunotherapy
have
focused
on
targeting
cellular
metabolism,
as
metabolic
characteristics
cells
can
directly
influence
activity
metabolism
cells,
particularly
T
cells.
Although
pathways
various
been
extensively
reviewed,
intersections
these
pathways,
their
potential
use
targets
for
improving
immune-checkpoint
blockade
therapies,
are
not
completely
understood.
This
review
focuses
interplay
between
tumor
metabolites
T-cell
dysfunction
well
relationship
several
patterns
activity/function
immunology.
Understanding
relationships
could
offer
new
avenues
basis.
Oncotarget,
Год журнала:
2025,
Номер
16(1), С. 337 - 346
Опубликована: Май 19, 2025
Different
treatment
strategies
are
required
for
the
non-muscle-invasive,
muscle-invasive,
and
metastatic
stages
of
bladder
cancer.
Standard
treatments
include
surgery,
chemotherapy,
radiation;
however,
they
have
their
limitations.
New
discoveries
shown
that
combining
immunotherapy
radiation
may
improve
patient
outcomes.
Radiation
therapy
promotes
immunogenic
cell
death,
which
leads
to
antigen
release
immune
activation,
whereas
enhances
system's
ability
recognize
destroy
cancer
cells
by
targeting
checkpoint
pathways
like
PD-1/PD-L1
CTLA-4.
This
review
examines
synergistic
mechanisms
diverse
modalities,
focusing
on
capacity
alter
tumor
microenvironment
elicit
systemic
anti-tumor
responses,
such
as
abscopal
effect.
Key
clinical
trials,
BTCRC-GU15-023
ANZUP,
demonstrated
efficacy
safety
these
medications.
However,
difficulties
persist,
overlapping
toxicities,
unpredictability
in
a
lack
accurate
selection
markers.
Large-scale
randomized
trials
needed
future
fine-tune
procedures,
minimize
toxicity,
validate
predictive
biomarkers
PD-L1
expression
mutation
burden.
By
addressing
hurdles,
combination
has
potential
change
therapeutic
landscape.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Май 5, 2023
Bladder
cancer
is
one
of
the
common
malignant
urothelial
tumors.
Post-translational
modification
(PTMs),
including
ubiquitination,
acetylation,
methylation,
and
phosphorylation,
have
been
revealed
to
participate
in
bladder
initiation
progression.
Ubiquitination
PTM,
which
conducted
by
E1
ubiquitin-activating
enzyme,
E2
ubiquitin-conjugating
enzyme
E3
ubiquitin-protein
ligase.
ubiquitin
ligases
play
a
key
role
oncogenesis
progression
drug
resistance
cancer.
Therefore,
this
review,
we
summarize
current
knowledge
regarding
functions
development.
Moreover,
provide
evidence
regulation
immunotherapy
Furthermore,
mention
multiple
compounds
that
target
improve
therapy
efficacy
We
hope
our
review
can
stimulate
researchers
clinicians
investigate
whether
how
targeting
acts
novel
strategy
for
therapy.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Ноя. 4, 2024
As
an
immune-related
tumor
type,
bladder
cancer
has
been
attracting
much
attention
in
the
study
of
its
markers.
In
recent
years,
researchers
have
made
rapid
progress
markers
for
cancer.
Studies
shown
that
play
important
role
diagnosis,
prognosis
assessment
and
treatment
addition,
detection
can
also
be
used
to
evaluate
efficacy
immunotherapy
predict
response
patients.
Therefore,
depth
expression
their
application
clinic
is
great
significance
expected
provide
new
breakthroughs
individualized
Future
studies
will
focus
more
on
how
detect
with
low
cost
high
accuracy,
as
well
develop
immunotherapeutic
strategies
bring
better
therapeutic
outcomes
Bacillus
Calmette-Guérin
(BCG)
therapy
for
patients
with
non-muscle
invasive
bladder
cancer
(NMIBC)
faces
limitations
in
efficacy
and
significant
side
effects,
aggravated
by
a
recent
global
shortage.
In
this
prospective
clinical
study,
we
report
outcomes
of
sequential
intravesical
adminis-tration
gemcitabine
docetaxel
(Gem/Doce)
as
the
first-line
treatment
BCG-naïve
high-risk
NMIBC
(HR
NMIBC).
From
October
2019
until
April
2022,
enrolled
52
followed
protocol
set
University
Iowa.
Follow-up
assessments
were
con-ducted
every
3
months.
cohort,
25
(48.1%)
diagnosed
T1HG
cancer,
10
(19.2%)
had
carcinoma
situ
(CIS),
17
(32.7%)
combination
CIS+T1HG.
Median
time
to
first
recurrence
T1HG,
CIS
T1HG+CIS
groups
was
11,
10.5
8.8
months,
respectively.
The
recurrence-free
survival
98.1%,
94.2%
80.8%
at
6,
9
12
rate
progression-free
100%,
98.1%
92.3%
We
demonstrated
safety
Gem/Doce
HR
during
one-year
follow-up.
Further
research
extended
follow-up,
well
direct
comparison
other
anticancer
agents,
are
essential.
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer,
Год журнала:
2024,
Номер
1879(5), С. 189123 - 189123
Опубликована: Май 26, 2024
Bacillus
Calmette-Guérin
(BCG)
treatment
for
non-muscle
invasive
bladder
cancer
(NMIBC)
is
an
established
immunotherapeutic,
however,
a
significant
portion
of
patients
do
not
respond
to
treatment.
Despite
extensive
research
into
the
therapeutic
mechanism
BCG,
gaps
remain
in
our
understanding.
This
review
specifically
focuses
on
epigenomic
contributions
immune
microenvironment,
context
BCG
NMIBC.
We
also
summarise
current
understanding
NMIBC
epigenetic
characteristics,
and
discuss
how
future
targeted
strategies
therapy
should
incorporate
both
biomarkers
conjunction
with
genomic
biomarkers.