Clinical Epigenetics,
Год журнала:
2025,
Номер
17(1)
Опубликована: Март 21, 2025
Immunotherapy,
particularly
immune
checkpoint
inhibitor
therapy,
has
demonstrated
clinical
benefits
in
solid
tumours.
Despite
its
satisfactory
efficacy,
it
still
faces
several
issues,
such
as
limited
eligibility,
low
response
rates
and
cytotoxicity.
Cancer
epigenetics
implies
that
tumour
cells
exhibit
unique
phenotypes
because
of
their
characteristics,
thus
reprogramming
the
epigenome
holds
promise
for
cancer
therapy.
Epigenetic
regulation
plays
an
important
role
regulating
gene
expression
during
development
maintenance.
regulators
induce
cell
cycle
arrest,
apoptosis
differentiation
cells,
thereby
exerting
anti-tumour
effects.
Recent
studies
have
revealed
a
significant
correlation
between
epigenetic
regulatory
factors
Epigenetics
can
modulate
various
aspects
microenvironment
to
enhance
sensitivity
immunotherapy,
lowering
concentration
required
mitigating
This
review
primarily
discusses
DNA
methyltransferase
inhibitors,
histone
deacetylase
enhancer
zeste
homolog
2
inhibitors
lysine-specific
demethylase
1
which
are
associated
with
transcriptional
repression.
repression
alters
genes
involved
checkpoint,
enhancing
effectiveness
immunotherapy.
We
also
discuss
potential
challenges
immunotherapy
highlight
advantages,
application
research
on
integrating
B
lymphocytes
are
essential
mediators
of
humoral
immunity
and
play
multiple
roles
in
human
cancer.
To
decode
the
functions
tumor-infiltrating
cells,
we
generated
a
cell
blueprint
encompassing
single-cell
transcriptome,
cell-receptor
repertoire,
chromatin
accessibility
data
across
20
different
cancer
types
(477
samples,
269
patients).
cells
harbored
extraordinary
heterogeneity
comprised
15
subsets,
which
could
be
grouped
into
two
independent
developmental
paths
(extrafollicular
versus
germinal
center).
Tumor
extrafollicular
pathway
were
linked
with
worse
clinical
outcomes
resistance
to
immunotherapy.
The
dysfunctional
program
was
associated
glutamine-derived
metabolites
through
epigenetic-metabolic
cross-talk,
promoted
T
cell-driven
immunosuppressive
program.
These
suggest
an
intratumor
balance
between
germinal-center
responses
that
possibly
harnessed
for
cell-targeting
Cell,
Год журнала:
2024,
Номер
187(17), С. 4790 - 4811.e22
Опубликована: Июль 23, 2024
Characterizing
the
compositional
and
phenotypic
characteristics
of
tumor-infiltrating
B
cells
(TIBs)
is
important
for
advancing
our
understanding
their
role
in
cancer
development.
Here,
we
establish
a
comprehensive
resource
human
by
integrating
single-cell
RNA
sequencing
data
from
649
patients
across
19
major
types.
We
demonstrate
substantial
heterogeneity
total
abundance
subtype
composition
observe
immunoglobulin
G
(IgG)-skewness
antibody-secreting
cell
isotypes.
Moreover,
identify
stress-response
memory
tumor-associated
atypical
(TAABs),
two
tumor-enriched
subpopulations
with
prognostic
potential,
shared
pan-cancer
manner.
In
particular,
TAABs,
characterized
high
clonal
expansion
level
proliferative
capacity
as
well
close
interactions
activated
CD4
T
tumors,
are
predictive
immunotherapy
response.
Our
integrative
depicts
distinct
clinically
relevant
TIB
subsets,
laying
foundation
further
exploration
functional
commonality
diversity
cancer.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Фев. 18, 2025
Abstract
Breast
cancer,
characterized
by
unique
epidemiological
patterns
and
significant
heterogeneity,
remains
one
of
the
leading
causes
malignancy-related
deaths
in
women.
The
increasingly
nuanced
molecular
subtypes
breast
cancer
have
enhanced
comprehension
precision
treatment
this
disease.
mechanisms
tumorigenesis
progression
been
central
to
scientific
research,
with
investigations
spanning
various
perspectives
such
as
tumor
stemness,
intra-tumoral
microbiota,
circadian
rhythms.
Technological
advancements,
particularly
those
integrated
artificial
intelligence,
significantly
improved
accuracy
detection
diagnosis.
emergence
novel
therapeutic
concepts
drugs
represents
a
paradigm
shift
towards
personalized
medicine.
Evidence
suggests
that
optimal
diagnosis
models
tailored
individual
patient
risk
expected
are
crucial,
supporting
era
oncology
for
cancer.
Despite
rapid
advancements
increasing
emphasis
on
clinical
comprehensive
update
summary
panoramic
knowledge
related
disease
needed.
In
review,
we
provide
thorough
overview
global
status
including
its
epidemiology,
factors,
pathophysiology,
subtyping.
Additionally,
elaborate
latest
research
into
contributing
progression,
emerging
strategies,
long-term
management.
This
review
offers
valuable
insights
Cancer
Research,
thereby
facilitating
future
progress
both
basic
application.
The
metabolism
of
stearoyl-GPE
plays
a
key
role
in
the
liver
metastasis
gastric
cancer.
This
investigation
delves
into
mechanisms
underlying
intricate
tumor
microenvironment
(TME)
heterogeneity
triggered
by
stearoyl
cancer
with
(LMGC),
offering
novel
perspectives
for
LMGC.
Utilizing
Mendelian
randomization,
we
determined
that
significantly
contributes
to
progression
(GC).
Following
this,
bulk
transcriptome
analyses
and
single-cell
multiomics
techniques
investigate
roles
metabolism-related
genes,
particularly
NCOA4,
regulating
LMGC
TME.
Our
analysis
highlights
crucial
modulating
complex
LMGC,
impacting
monocyte
cells.
Through
sequencing
spatial
transcriptomics,
have
identified
metabolic
genes
specific
within
cell
population,
including
NCOA4.
Regarding
relationship
between
ferroptosis,
metabolism,
findings,
it
is
plausible
pathways
intersect
involved
ferroptosis.
Ferroptosis,
characterized
iron-dependent
lipid
peroxidation,
represents
regulated
form
death.
activity
Stearoyl-CoA
desaturase
(SCD),
critical
enzyme
has
been
associated
modulation
composition
susceptibility
Furthermore,
integral
cellular
processes
related
oxidative
stress
both
which
are
significant
factors
context
study
enhances
understanding
ferroptosis
promoting
its
regulation
heterogeneity.
In
addition,
this
deeper
dynamics
provides
basis
development
better
interventions
combat
metastasis.
Journal of Clinical Investigation,
Год журнала:
2025,
Номер
135(7)
Опубликована: Март 31, 2025
Tertiary
lymphoid
structures
(TLS)
in
the
tumor
microenvironment
(TME)
are
emerging
solid-tumor
indicators
of
prognosis
and
response
to
immunotherapy.
Considering
that
tumorigenesis
requires
metabolic
reprogramming
subsequent
TME
remodeling,
discovery
TLS
regulators
is
expected
produce
immunotherapeutic
targets.
To
identify
such
regulators,
we
constructed
a
metabolism-focused
sgRNA
library
performed
an
vivo
CRISPR
screening
orthotopic
lung
mouse
model.
Combined
with
The
Cancer
Genome
Atlas
database
analysis
TLS-related
hub
genes,
found
loss
Acat1
cells
sensitized
tumors
anti-PD1
treatment,
accompanied
by
increased
TME.
Mechanistic
studies
revealed
ACAT1
resulted
mitochondrial
protein
hypersuccinylation
subsequently
enhanced
oxidative
metabolism,
which
impeded
formation.
Elimination
ROS
NAC
or
knockdown
promoted
B
cell
aggregation
construction.
Consistently,
data
from
tissue
microassays
305
patients
cancer
showed
were
more
abundant
non-small
(NSCLC)
tissues
lower
expression.
Intratumoral
expression
was
associated
poor
immunotherapy
outcomes
NSCLC.
In
conclusion,
our
results
identified
as
regulator
promising
target
