Cholesterol effects on the tumor immune microenvironment: from fundamental concepts to mechanisms and implications
Frontiers in Oncology,
Journal Year:
2025,
Volume and Issue:
15
Published: April 9, 2025
In
many
cancers,
the
tumor
microenvironment
is
enriched
with
cholesterol
due
to
increased
biosynthesis
and
uptake
by
cancer
cells,
resulting
in
accumulation
of
cholesterol,
esters,
oxysterols
other
metabolites
various
functions.
These
molecules
serve
as
structural
components,
energy
sources
intracellular
signaling
mediators,
while
their
toxic
by-products
are
secreted
suppress
anti-tumor
immune
activity
prevent
lipid
peroxidation
that
could
induce
cell
apoptosis.
Immune
cells
also
contribute
dynamics.
Tumor-associated
macrophages
(TAMs)
release
support
metabolism,
myeloid-derived
suppressor
(MDSCs)
consume
essential
such
L-arginine,
which
impairs
T-cell
proliferation
activation.
Elevated
dendritic
migration
antigen
presentation
and,
lymphocytes,
favors
development
a
regulatory
T
(Treg)
phenotype
inhibits
antitumor
cytokines,
further
weakening
response.
findings
suggest
targeting
metabolism
promising
strategy
for
treatment,
improving
efficacy
checkpoint
blockade
(ICB)
therapies.
this
manuscript,
molecular
mechanisms
underlying
effects
on
landscape
reviewed
potential
cholesterol-lowering
drugs
enhance
responses
explored.
Language: Английский
Clinical potential and experimental validation of prognostic genes in hepatocellular carcinoma revealed by risk modeling utilizing single cell and transcriptome constructs
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: April 4, 2025
Background
Hepatocellular
carcinoma
(HCC)
is
the
leading
cause
of
tumor-related
mortality
worldwide.
There
an
urgent
need
for
predictive
biomarkers
to
guide
treatment
decisions.
This
study
aimed
identify
robust
prognostic
genes
HCC
and
establish
a
theoretical
foundation
clinical
interventions.
Methods
The
datasets
were
obtained
from
public
databases
then
differential
expression
analysis
used
obtain
significant
gene
profiles.
Subsequently,
univariate
Cox
regression
PH
assumption
test
performed,
risk
model
was
developed
using
optimal
algorithm
101
combinations
on
TCGA-LIHC
dataset
pinpoint
genes.
Immune
infiltration
drug
sensitivity
analyses
conducted
assess
impact
these
explore
potential
chemotherapeutic
agents
HCC.
Additionally,
single-cell
employed
key
cellular
players
their
interactions
within
tumor
microenvironment.
Finally,
reverse
transcription-quantitative
polymerase
chain
reaction
(RT-qPCR)
utilized
validate
roles
in
Results
A
total
eight
identified
(MCM10,
CEP55,
KIF18A,
ORC6,
KIF23,
CDC45,
CDT1,
PLK4).
model,
constructed
based
genes,
effective
predicting
survival
outcomes
patients.
CEP55
exhibited
strongest
positive
correlation
with
activated
CD4
T
cells.
top
10
drugs
showed
increased
low-risk
group.
B
cells
as
components
highest
interaction
numbers
strengths
macrophages
both
control
groups.
Prognostic
more
highly
expressed
initial
state
cell
differentiation.
RT-qPCR
confirmed
upregulation
MCM10,
PLK4
tissues
(p<
0.05).
Conclusion
successfully
PLK4),
which
provided
new
directions
exploring
pathogenesis
research
Language: Английский
Cholesterol Targeted Catalytic Hydrogel Fueled by Tumor Debris can Enhance Microwave Ablation Therapy and Anti‐Tumor Immune Response
Advanced Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 12, 2024
Abstract
The
immunosuppressive
residual
tumor
microenvironment
(IRTM)
is
a
key
factor
in
the
high
recurrence
and
metastasis
rates
of
hepatocellular
carcinoma
(HCC)
after
microwave
ablation
(MWA).
Cholesterol‐rich
fragments
significantly
contribute
to
IRTM
deterioration.
This
study
developed
cholesterol‐targeted
catalytic
hydrogel,
DA‐COD‐OD‐HCS,
enhance
synergy
between
MWA
immune
checkpoint
inhibitors
(ICIs)
for
HCC
treatment.
Cholesterol
oxidase
(COD),
modified
with
dimethyl
maleic
anhydride
(DA)
release
acidic
IRTM,
used
degrade
cholesterol.
Oxydextran
(OD)
hemin‐chitosan
(HCS)
formed
dual
network
gel,
ensuring
long‐term
fixation
COD
hemin
post‐MWA.
In
both
vitro
vivo
models,
DA‐COD‐OD‐HCS
effectively
released
COD,
degraded
cholesterol,
induced
cell
ferroptosis,
enhancing
antitumor
response.
Combined
anti‐PD‐L1
immunotherapy,
this
strategy
inhibited
primary
growth
distant
metastases,
without
side
effects
on
adjacent
tissues.
work
highlights
that
cholesterol‐targeting
hydrogels
fueled
by
debris
can
improve
efficacy
ICIs,
offering
novel
therapeutic
approach
HCC.
Language: Английский
The protective effect of Auricularia auricula polysaccharides on cyclophosphamide-induced immunosuppression and intestinal injury: A fecal microbiota transplantation study
Tianci Wang,
No information about this author
Zikun Jia,
No information about this author
Canghai An
No information about this author
et al.
Food Bioscience,
Journal Year:
2024,
Volume and Issue:
62, P. 105416 - 105416
Published: Nov. 5, 2024
Language: Английский
Protocol to detect immune levels, abnormal metabolism, and signaling pathways in tumor tissue based on scRNA-seq obtained from patient databases
STAR Protocols,
Journal Year:
2024,
Volume and Issue:
5(2), P. 103065 - 103065
Published: May 14, 2024
Malignant
tumor
cells
are
typically
more
active
in
terms
of
metabolism
and
signal
transduction
compared
to
immune
normal
cells.
Here,
we
present
a
protocol
evaluate
levels,
abnormal
metabolism,
signaling
pathways
tissue
based
on
single-cell
sequencing
patient
data
obtained
from
the
GEO
database.
We
describe
steps
for
microenvironment
(TIME)-based
evaluation,
purity
assessment,
identification
metabolic
pathways.
then
detail
procedures
screening
hub
genes.
For
complete
details
use
execution
this
protocol,
please
refer
Bai
et
al.1
Language: Английский
Protocol to develop a chemotherapy drug screening process by constructing a cancer prognostic model using public databases
STAR Protocols,
Journal Year:
2024,
Volume and Issue:
5(3), P. 103158 - 103158
Published: June 28, 2024
Drug
resistance
is
currently
the
biggest
challenge
in
cancer
chemotherapy.
Here,
we
present
a
protocol
to
develop
chemotherapy
drug
screening
process
by
constructing
prognostic
model
(PM)
using
public
databases.
We
describe
steps
for
downloading
code
and
data,
preparing
expression
matrix
metadata
analysis,
modeling
genes,
PM.
then
detail
procedures
predictive
websites
patients'
survival
based
on
their
age,
tumor
stage,
gene
levels,
risk
scores.
For
complete
details
use
execution
of
this
protocol,
please
refer
Bai
et
al.
Language: Английский
Overexpression pattern, function, and clinical value of proteasome 26S subunit non-ATPase 6 in hepatocellular carcinoma
Shengsheng Zhou,
No information about this author
Yuping Ye,
No information about this author
Yi Chen
No information about this author
et al.
World Journal of Clinical Oncology,
Journal Year:
2024,
Volume and Issue:
16(2)
Published: Dec. 11, 2024
In
recent
years,
many
studies
have
shown
that
proteasome
26S
subunit
non-ATPase
6
(PSMD6)
plays
an
important
role
in
the
occurrence
and
development
of
malignant
tumours.
Unfortunately,
there
are
no
reports
on
evaluation
potential
PSMD6
hepatocellular
carcinoma
(HCC).
To
comprehensively
evaluate
overexpression
pattern
clinical
significance
HCC
tissues.
This
study
integrated
mRNA
expression
profiles
from
4672
3667
non-HCC
tissues,
along
with
immunohistochemical
scores
383
adjacent
to
assess
HCC.
Clustered
regularly
interspaced
short
palindromic
repeats
knockout
technology
evaluated
PSMD6's
essential
cell
growth.
Functional
enrichment
analysis
explored
molecular
mechanism
abnormalities
Drug
sensitivity
docking
analysed
effect
abnormal
drug
cells.
The
results
41
external
two
internal
datasets
showed
(SMD
=
0.26,
95%CI:
0.09-0.42,
P
<
0.05)
protein
2.85,
1.19-4.50,
were
significantly
overexpressed
had
a
significant
tissues
0.40,
0.15-0.66,
0.05).
inhibited
growth
(chronos
-1).
implicated
ribosome
biogenesis
RNA
splicing.
Significant
signalling
pathways
such
as
degradation,
ribosomes,
chemical
carcinogenesis-reactive
oxygen
species.
model
high
was
associated
tolerance
cells
drugs
ML323,
sepantronium
bromide,
GDC0810.
Overexpressed
effectively
distinguished
(AUC
0.75,
0.71-0.79).
first
discover
is
for
may
be
involved
Language: Английский