Advanced Functional Materials,
Год журнала:
2023,
Номер
33(49)
Опубликована: Сен. 3, 2023
Abstract
The
complex
physiological
environment
in
bone
tissue
poses
a
challenge
to
the
efficient
delivery
of
chemotherapeutic
agents
for
osteosarcoma
(OS)
treatment;
hence,
an
drug
system
designed
OS
is
highly
desired.
Herein,
alendronate
(Ale)‐based
cationic
platinum
prodrug
nanoparticles
(Ale
NP)
are
developed,
which
exhibit
cascade
responsiveness
tumor
microenvironment.
With
Ale
triggered
targeting
and
charge
reversal
effects,
NP
demonstrates
superior
capacity
achieving
deep
penetration
into
dense
tissues.
Furthermore,
can
induce
dendritic
cell
(DC)
maturation
via
activation
cyclic
GMP‐AMP
synthase‐stimulator
interferon
genes
(cGAS‐STING)
pathway
using
drugs.
potent
phenanthridine
(Pt(II))
be
released
presence
overexpressed
glutathione
(GSH)
cells,
thereby
dual‐targeted
drugs
OS.
Notably,
not
only
effectively
eliminates
internal
region
but
also
acts
as
STING
agonist
reverse
suppressive
microenvironment
Overall,
Ale‐triggered
dual‐cascade
significantly
improve
OS,
hence
paving
promising
avenue
clinical
treatment
Cancer Discovery,
Год журнала:
2024,
Номер
14(3), С. 468 - 491
Опубликована: Янв. 4, 2024
Abstract
Activating
innate
immunity
in
cancer
cells
through
cytoplasmic
nucleic
acid
sensing
pathways,
a
phenomenon
known
as
“viral
mimicry,”
has
emerged
an
effective
strategy
to
convert
immunologically
“cold”
tumors
into
“hot.”
Through
curated
CRISPR-based
screen
of
RNA
helicases,
we
identified
DExD/H-box
helicase
9
(DHX9)
potent
repressor
double-stranded
(dsRNA)
small
cell
lung
cancers
(SCLC).
Depletion
DHX9
induced
accumulation
dsRNA
and
triggered
tumor-intrinsic
immunity.
Intriguingly,
ablating
also
aberrant
R-loops,
which
resulted
increase
DNA
damage–derived
replication
stress
SCLCs.
In
vivo,
deletion
promoted
decrease
tumor
growth
while
inducing
more
immunogenic
microenvironment,
invigorating
responsiveness
immune-checkpoint
blockade.
These
findings
suggest
that
is
crucial
stress,
representing
promising
target
for
SCLC
other
genomic
instability
contributes
pathology.
Significance:
One
trigger
immune
response
within
enhance
immunotherapy
efficacy
by
endogenous
“virus-mimetic”
accumulation.
Here,
identify
viral-mimicry-inducing
factor
involved
the
suppression
RNAs
R-loops
propose
novel
antitumor
See
related
commentary
Chiappinelli,
p.
389.
This
article
featured
Selected
Articles
from
Issue,
384
Cancer Cell,
Год журнала:
2024,
Номер
42(7), С. 1268 - 1285.e7
Опубликована: Июль 1, 2024
Expanding
the
efficacy
of
immune
checkpoint
blockade
(ICB)
in
colorectal
cancer
(CRC)
presses
for
a
comprehensive
understanding
treatment
responsiveness.
Here,
we
analyze
multiple
sequential
single-cell
samples
from
22
patients
undergoing
PD-1
to
map
evolution
local
and
systemic
immunity
CRC
patients.
In
tumors,
identify
coordinated
cellular
programs
exhibiting
distinct
response
associations.
Specifically,
exhausted
T
(Tex)
or
tumor-reactive-like
CD8+
(Ttr-like)
cells
are
closely
related
efficacy,
Tex
show
correlated
proportion
changes
with
other
tumor-enriched
cell
types
following
blockade.
addition,
reveal
less-exhausted
phenotype
blood-associated
Ttr-like
tumors
find
that
their
higher
abundance
suggests
better
outcomes.
Finally,
major
histocompatibility
complex
(MHC)
II-related
signature
circulating
at
baseline
is
linked
superior
responses.
Our
study
provides
insights
into
spatiotemporal
dynamics
neoadjuvant
CRC.
ACS Nano,
Год журнала:
2024,
Номер
18(15), С. 10542 - 10556
Опубликована: Апрель 1, 2024
Immunotherapy
has
emerged
as
a
potential
approach
for
breast
cancer
treatment.
However,
the
rigid
stromal
microenvironment
and
low
immunogenicity
of
tumors
strongly
reduce
sensitivity
to
immunotherapy.
To
sensitize
patients
immunotherapy,
hyaluronic
acid-modified
zinc
peroxide–iron
nanocomposites
(Fe-ZnO2@HA,
abbreviated
FZOH)
were
synthesized
remodel
increase
tumor
immunogenicity.
The
constructed
FZOH
spontaneously
generated
highly
oxidative
hydroxyl
radicals
(·OH)
that
degrade
acid
(HA)
in
extracellular
matrix
(ECM),
thereby
reshaping
enhancing
blood
perfusion,
drug
penetration,
immune
cell
infiltration.
Furthermore,
not
only
triggers
pyroptosis
through
activation
caspase-1/GSDMD-dependent
pathway
but
also
induces
ferroptosis
various
mechanisms,
including
increasing
levels
Fe2+
intracellular
iron
pool,
downregulating
expression
FPN1
inhibit
efflux,
activating
p53
signaling
cause
failure
SLC7A11-GSH-GPX4
axis.
Upon
treatment
with
FZOH,
4T1
cells
undergo
both
pyroptosis,
exhibiting
strong
immunogenic
response.
remodeling
response
induced
by
collectively
compensate
limitations
immunotherapy
significantly
enhance
antitumor
checkpoint
inhibitor
αPD-1.
This
study
proposes
perspective
therapy
cancer.
Journal of Experimental & Clinical Cancer Research,
Год журнала:
2024,
Номер
43(1)
Опубликована: Фев. 2, 2024
Abstract
Tumor-infiltrating
T
cells
recognize,
attack,
and
clear
tumor
cells,
playing
a
central
role
in
antitumor
immune
response.
However,
certain
can
impair
this
response
help
escape.
Therefore,
exploring
the
factors
that
influence
T-cell
infiltration
is
crucial
to
understand
immunity
improve
therapeutic
effect
of
cancer
immunotherapy.
The
use
single-cell
RNA
sequencing
(scRNA-seq)
allows
high-resolution
analysis
precise
composition
with
different
phenotypes
other
microenvironmental
factors,
including
non-immune
stromal
related
molecules
microenvironment
various
types.
In
review,
we
summarized
research
progress
on
crosstalk
cytokines
during
using
scRNA-seq
provide
insights
into
mechanisms
regulating
contribute
new
perspectives
Tumor
microenvironment
(TME)-induced
nanocatalytic
therapy
is
a
promising
strategy
for
cancer
treatment,
but
the
low
catalytic
efficiency
limits
its
therapeutic
efficacy.
Single-atom
catalysts
(SACs)
are
new
type
of
nanozyme
with
incredible
efficiency.
Here,
single-atom
manganese
(Mn)-N/C
constructed.
Mn-N/C
catalyzes
conversion
cellular
H
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Март 13, 2024
Immune
Checkpoint
Inhibitors
(ICIs)
therapy
has
advanced
significantly
in
treating
malignant
tumors,
though
most
'cold'
tumors
show
no
response.
This
resistance
mainly
arises
from
the
varied
immune
evasion
mechanisms.
Hence,
understanding
transformation
to
'hot'
is
essential
developing
effective
cancer
treatments.
Furthermore,
tumor
profiling
critical,
requiring
a
range
of
diagnostic
techniques
and
biomarkers
for
evaluation.
The
success
immunotherapy
relies
on
T
cells'
ability
recognize
eliminate
cells.
In
absence
cell
infiltration
leads
ineffectiveness
ICI
therapy.
Addressing
these
challenges,
especially
impairment
activation
homing,
crucial
enhance
therapy's
efficacy.
Concurrently,
strategies
convert
into
ones,
including
boosting
adoptive
therapies
such
as
cell-recruiting
bispecific
antibodies
Chimeric
Antigen
Receptor
(CAR)
cells,
are
under
extensive
exploration.
Thus,
identifying
key
factors
that
impact
vital
creating
treatments
targeting
tumors.
Experimental Hematology and Oncology,
Год журнала:
2024,
Номер
13(1)
Опубликована: Авг. 6, 2024
Abstract
The
tumor
microenvironment
demonstrates
great
immunophenotypic
heterogeneity,
which
has
been
leveraged
in
traditional
immune-hot/cold
categorization
based
on
the
abundance
of
intra-tumoral
immune
cells.
By
incorporating
spatial
contexture,
immunophenotype
was
further
elaborated
into
immune-inflamed,
immune-excluded,
and
immune-desert.
However,
mechanisms
underlying
these
different
phenotypes
are
yet
to
be
comprehensively
elucidated.
In
this
review,
we
discuss
how
cells
interact
collectively
shape
landscape
from
perspectives
cells,
extracellular
matrix,
cancer
metabolism,
summarize
potential
therapeutic
options
according
distinct
immunophenotypes
for
personalized
precision
medicine.
Journal for ImmunoTherapy of Cancer,
Год журнала:
2025,
Номер
13(1), С. e009140 - e009140
Опубликована: Янв. 1, 2025
The
efficacy
of
immune
checkpoint
inhibitors
(ICIs)
depends
on
the
tumor
microenvironment
(TIME),
with
a
preference
for
T
cell-inflamed
TIME.
However,
challenges
in
tissue-based
assessments
via
biopsies
have
triggered
exploration
non-invasive
alternatives,
such
as
radiomics,
to
comprehensively
evaluate
TIME
across
diverse
cancers.
To
address
these
challenges,
we
develop
an
ICI
response
signature
by
integrating
radiomics
gene-expression
profiles.
We
conducted
pan-cancer
investigation
into
utility
assessment,
including
1360
tumors
from
428
patients.
Leveraging
contrast-enhanced
CT
images,
characterized
through
RNA
gene
expression
analysis,
using
signature.
Subsequently,
CT-radiomic
predicting
inflamed
(CT-TIME)
was
developed
and
externally
validated.
Machine
learning
employed
select
robust
radiomic
features
predict
study
also
integrated
independent
cohorts
longitudinal
baseline
biopsies,
comprehensive
immunohistochemistry
panel
evaluation
assess
biological
associations,
spatiotemporal
landscape
clinical
CT-TIME.
CT-TIME
signature,
comprising
four
linked
T-cell
microenvironment,
demonstrated
performance
AUCs
(95%
CI)
0.85
(0.73
0.96)
(training)
0.78
(0.65
0.92)
(external
validation).
scores
exhibited
positive
correlations
CD3,
CD8,
CD163
expression.
Intrapatient
analysis
revealed
considerable
heterogeneity
between
tumors,
which
could
not
be
assessed
biopsies.
Evaluation
aggregated
per-patient
highlighted
its
promising
dynamically
assessing
immunotherapy
scenarios
advanced
cancer.
Despite
demonstrating
progression
disease
at
first
follow-up,
patients
within
status
group,
identified
CT-TIME,
significantly
prolonged
progression-free
survival
(PFS),
some
surpassing
5
months,
suggesting
potential
phenomenon
pseudoprogression.
Cox
models
images
statistically
significant
reduction
risk
PFS
cohort
(HR
0.62,
95%
CI
0.44
0.88,
p=0.007),
Kaplan-Meier
further
confirmed
substantial
differences
uninflamed
(log-rank
test
p=0.009).
holds
promise
impacting
decision-making,
patient
stratification,
treatment
outcomes
therapies.