Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Feb. 6, 2024
Abstract
Immunotherapy
with
immune
checkpoint
blockade
(ICB)
for
glioblastoma
(GBM)
is
promising
but
its
clinical
efficacy
seriously
challenged
by
the
blood-tumor
barrier
(BTB)
and
immunosuppressive
tumor
microenvironment.
Here,
anti-programmed
death-ligand
1
antibodies
(aPD-L1)
are
loaded
into
a
redox-responsive
micelle
ICB
further
amplified
paclitaxel
(PTX)-induced
immunogenic
cell
death
(ICD)
via
co-encapsulation
approach
reinvigoration
of
local
anti-GBM
responses.
Consequently,
micelles
cross
BTB
retained
in
reductive
microenvironment
without
altering
bioactivity
aPD-L1.
The
enhanced
aPD-L1
PTX
combination
suppression
primary
recurrent
GBM,
accumulation
cytotoxic
T
lymphocytes,
induction
long-lasting
immunological
memory
orthotopic
GBM-bearing
mice.
facilitating
efficient
antibody
delivery
combining
chemotherapeutic
agent-induced
ICD
demonstrate
that
chemo-immunotherapy
might
reprogram
immunity
to
empower
immunotherapy
against
GBM.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Oct. 10, 2022
Brain
metastases
(BrMs)
are
a
common
occurrence
in
lung
cancer
with
dismal
outcome.
To
understand
the
mechanism
of
metastasis
to
inform
prognosis
and
treatment,
here
we
analyze
primary
metastasized
tumor
specimens
from
44
non-small
cell
patients
by
spatial
RNA
sequencing,
affording
whole
transcriptome
map
resolved
morphological
markers
for
core,
immune
microenvironment
(TIME),
brain
(TBME).
Our
data
indicate
that
(TME)
brain,
including
TIME
TBME,
undergoes
extensive
remodeling
create
an
immunosuppressive
fibrogenic
niche
BrMs.
Specifically,
TME
is
characterized
reduced
antigen
presentation
B/T
function,
increased
neutrophils
M2-type
macrophages,
immature
microglia,
reactive
astrocytes.
Differential
gene
expression
network
analysis
identify
fibrosis
regulation
as
major
functional
modules
disrupted
both
TME.
Besides
providing
systems-level
insights
into
metastasis,
our
study
uncovers
potential
prognostic
biomarkers
suggests
therapeutic
strategies
should
be
tailored
status
Nature Medicine,
Journal Year:
2022,
Volume and Issue:
28(1), P. 125 - 135
Published: Jan. 1, 2022
Abstract
Cancers
arising
from
germline
DNA
mismatch
repair
deficiency
or
polymerase
proofreading
(MMRD
and
PPD)
in
children
harbour
the
highest
mutational
microsatellite
insertion–deletion
(MS-indel)
burden
humans.
MMRD
PPD
cancers
are
commonly
lethal
due
to
inherent
resistance
chemo-irradiation.
Although
immune
checkpoint
inhibitors
(ICIs)
have
failed
benefit
previous
studies,
we
hypothesized
that
hypermutation
caused
by
will
improve
outcomes
following
ICI
treatment
these
patients.
Using
an
international
consortium
registry
study,
report
on
of
45
progressive
recurrent
tumors
38
Durable
objective
responses
were
observed
most
patients,
culminating
a
3
year
survival
41.4%.
High
mutation
predicted
response
for
ultra-hypermutant
(>100
mutations
per
Mb)
enriched
combined
+
PPD,
while
MS-indels
with
lower
(10–100
Mb).
Furthermore,
both
mechanisms
associated
increased
infiltration
even
‘immunologically
cold’
such
as
gliomas,
contributing
favorable
response.
Pseudo-progression
(flare)
was
common
activation
tumor
microenvironment
systemically.
patients
flare
who
continued
achieved
durable
responses.
This
study
demonstrates
improved
not
previously
known
respond
treatment,
including
central
nervous
system
synchronous
cancers,
identifies
dual
roles
predicting
sustained
immunotherapy.
Journal of Clinical Investigation,
Journal Year:
2022,
Volume and Issue:
132(8)
Published: Feb. 24, 2022
Tumor
Treating
Fields
(TTFields),
an
approved
therapy
for
glioblastoma
(GBM)
and
malignant
mesothelioma,
employ
noninvasive
application
of
low-intensity,
intermediate-frequency,
alternating
electric
fields
to
disrupt
the
mitotic
spindle,
leading
chromosome
missegregation
apoptosis.
Emerging
evidence
suggests
that
TTFields
may
also
induce
inflammation.
However,
mechanism
underlying
this
property
whether
it
can
be
harnessed
therapeutically
are
unclear.
Here,
we
report
induced
focal
disruption
nuclear
envelope,
cytosolic
release
large
micronuclei
clusters
intensely
recruited
activated
2
major
DNA
sensors
—
cyclic
GMP-AMP
synthase
(cGAS)
absent
in
melanoma
(AIM2)
their
cognate
cGAS/stimulator
interferon
genes
(STING)
AIM2/caspase
1
inflammasomes
produce
proinflammatory
cytokines,
type
interferons
(T1IFNs),
T1IFN-responsive
genes.
In
syngeneic
murine
GBM
models,
TTFields-treated
cells
antitumor
memory
immunity
a
cure
rate
42%
66%
STING-
AIM2-dependent
manner.
Using
single-cell
bulk
RNA
sequencing
peripheral
blood
mononuclear
cells,
detected
robust
post-TTFields
activation
adaptive
patients
with
via
T1IFN-based
trajectory
identified
gene
panel
signature
effects
on
T
cell
clonal
expansion.
Collectively,
these
studies
defined
therapeutic
strategy
using
as
cancer
immunotherapy
potentially
other
solid
tumors.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Sept. 7, 2023
Gliomas
are
the
most
prevalent
primary
malignant
brain
tumors
worldwide,
with
glioblastoma
(GBM)
being
common
and
aggressive
type.
Despite
two
decades
of
relentless
pursuit
in
exploring
novel
therapeutic
approaches
for
GBM,
there
is
limited
progress
improving
patients’
survival
outcomes.
Numerous
obstacles
impede
effective
treatment
including
immunosuppressive
tumor
microenvironment
(TME),
blood-brain
barrier,
extensive
heterogeneity.
these
challenges,
immunotherapies
emerging
as
a
promising
avenue
that
may
offer
new
hope
gliomas.
There
four
main
types
gliomas,
immune
checkpoint
blockades,
chimeric
antigen
receptor
T-cell
therapies,
vaccines,
oncolytic
viruses.
In
addition,
gene
therapy,
bispecific
antibody
combine
therapy
also
briefly
introduced
this
review.
The
significant
role
TME
process
has
been
emphasized
many
studies.
Although
immunotherapy
enormous
effort
required
to
overcome
existing
barriers
its
success.
Owing
rapid
development
increasing
attention
paid
article
aims
review
recent
advances
Cell,
Journal Year:
2023,
Volume and Issue:
186(21), P. 4546 - 4566.e27
Published: Sept. 27, 2023
Neutrophils
are
abundant
immune
cells
in
the
circulation
and
frequently
infiltrate
tumors
substantial
numbers.
However,
their
precise
functions
different
cancer
types
remain
incompletely
understood,
including
brain
microenvironment.
We
therefore
investigated
neutrophils
tumor
tissue
of
glioma
metastasis
patients,
with
matched
peripheral
blood,
herein
describe
first
in-depth
analysis
neutrophil
phenotypes
these
tissues.
Orthogonal
profiling
strategies
humans
mice
revealed
that
tumor-associated
(TANs)
differ
significantly
from
blood
have
a
prolonged
lifespan
immune-suppressive
pro-angiogenic
capacity.
TANs
exhibit
distinct
inflammatory
signature,
driven
by
combination
soluble
mediators
necrosis
factor
alpha
(TNF-ɑ)
Ceruloplasmin,
which
is
more
pronounced
versus
glioma.
Myeloid
cells,
macrophages,
emerge
at
core
this
network
pro-inflammatory
mediators,
supporting
concept
critical
myeloid
niche
regulating
overall
suppression
human
tumors.
ACS Nano,
Journal Year:
2023,
Volume and Issue:
17(23), P. 23746 - 23760
Published: Nov. 22, 2023
The
increasing
understanding
of
ferroptosis
has
indicated
its
role
and
therapeutic
potential
in
cancer;
however,
this
knowledge
yet
to
be
translated
into
effective
therapies.
Glioblastoma
(GBM)
patients
face
a
bleak
prognosis
encounter
challenges
due
the
limited
treatment
options
available.
In
study,
we
conducted
genome-wide
CRISPR–Cas9
screening
presence
inducer
(RSL3)
identify
key
driver
genes
involved
ferroptosis.
We
identified
ALOX15,
lipoxygenase
(LOX),
as
an
essential
Small
activating
RNA
(saRNA)
was
used
mediate
expression
ALOX15
promoted
GBM
cells.
then
coated
saALOX15-loaded
mesoporous
polydopamine
(MPDA)
with
Angiopep-2-modified
macrophage
membranes
(MMs)
reduce
clearance
by
mononuclear
phagocyte
system
(MPS)
increase
ability
complex
cross
blood–brain
barrier
(BBB)
during
specific
targeted
therapy
orthotopic
GBM.
These
generated
hybrid
nanoparticles
(NPs)
induced
mediating
mitochondrial
dysfunction
rendering
morphology
abnormal.
vivo,
modified
MM
enabled
NPs
target
cells,
exert
marked
inhibitory
effect
on
progression,
promote
radiosensitivity.
Our
results
reveal
promising
suggest
biomimetic
strategy
that
depends
biological
properties
MMs
enhance
vivo
performance
for
treating
Journal of Hematology & Oncology,
Journal Year:
2024,
Volume and Issue:
17(1)
Published: May 8, 2024
Abstract
Glioblastoma
(GBM),
the
predominant
and
primary
malignant
intracranial
tumor,
poses
a
formidable
challenge
due
to
its
immunosuppressive
microenvironment,
thereby
confounding
conventional
therapeutic
interventions.
Despite
established
treatment
regimen
comprising
surgical
intervention,
radiotherapy,
temozolomide
administration,
exploration
of
emerging
modalities
such
as
immunotherapy
integration
medicine
engineering
technology
therapy,
efficacy
these
approaches
remains
constrained,
resulting
in
suboptimal
prognostic
outcomes.
In
recent
years,
intensive
scrutiny
inhibitory
milieu
within
GBM
has
underscored
significance
cellular
constituents
microenvironment
their
interactions
with
cells
neurons.
Novel
immune
targeted
therapy
strategies
have
emerged,
offering
promising
avenues
for
advancing
treatment.
One
pivotal
mechanism
orchestrating
immunosuppression
involves
aggregation
myeloid-derived
suppressor
(MDSCs),
glioma-associated
macrophage/microglia
(GAM),
regulatory
T
(Tregs).
Among
these,
MDSCs,
though
constituting
minority
(4–8%)
CD45
+
GBM,
play
central
component
fostering
evasion
propelling
tumor
progression,
angiogenesis,
invasion,
metastasis.
MDSCs
deploy
intricate
mechanisms
that
adapt
dynamic
(TME).
Understanding
interplay
between
provides
compelling
basis
This
review
seeks
elucidate
inherent
explore
existing
targets,
consolidate
insights
into
MDSC
induction
contribution
immunosuppression.
Additionally,
comprehensively
surveys
ongoing
clinical
trials
potential
strategies,
envisioning
future
where
targeting
could
reshape
landscape
GBM.
Through
synergistic
other
modalities,
this
approach
can
establish
multidisciplinary,
multi-target
paradigm,
ultimately
improving
prognosis
quality
life
patients
