Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Апрель 27, 2023
Abstract
Glioblastoma
(GBM)
is
the
most
common
malignant
brain
tumor
and
has
“immunologically
cold”
features.
Changing
GBM
to
an
hot”
requires
a
strong
trigger
that
induces
initial
immune
responses
in
GBM.
Allogeneic
natural
killer
cells
(NKCs)
have
gained
considerable
attention
as
promising
immunotherapeutic
tools
against
cancer,
where
gene-edited
NKCs
would
result
effective
anti-cancer
treatment.
The
present
study
focused
on
checkpoint
molecule
cytokine-inducible
SH2-containing
protein
(CIS)
critical
negative
regulator
NKCs.
We
successfully
induced
human
CIS-deleted
(NK
dCIS)
by
combining
our
specific
NKC
expansion
method
available
for
clinical
application
genome
editing
technology.
CIS
gene-specific
guide
RNA/Cas9
complex
suppressed
expression
expanded
with
high
efficacy.
Comprehensive
gene
analysis
demonstrated
increased
of
265
genes
decreased
86
NK
dCIS,
which
were
comparatively
small
changes.
Gene
set
enrichment
revealed
enriched
involved
effector
functions.
Functional
dCIS
had
interferon
(IFN)ɤ
necrosis
factor
(TNF)
production.
deletion
enhanced
NKC-mediated
apoptosis
induction
allogeneic
spheroids.
Intracranial
administration
prolonged
overall
survival
xenograft
mice.
Furthermore,
extended
findings
successful
primary
CRISPR/Cas9
efficient
expansion.
anti-tumor
effects
could
be
alternative
patients
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(5), С. 2529 - 2529
Опубликована: Фев. 21, 2024
Glioblastoma
(GB)
stands
out
as
the
most
prevalent
and
lethal
form
of
brain
cancer.
Although
great
efforts
have
been
made
by
clinicians
researchers,
no
significant
improvement
in
survival
has
achieved
since
Stupp
protocol
became
standard
care
(SOC)
2005.
Despite
multimodality
treatments,
recurrence
is
almost
universal
with
rates
under
2
years
after
diagnosis.
Here,
we
discuss
recent
progress
our
understanding
GB
pathophysiology,
particular,
importance
glioma
stem
cells
(GSCs),
tumor
microenvironment
conditions,
epigenetic
mechanisms
involved
growth,
aggressiveness
recurrence.
The
discussion
on
therapeutic
strategies
first
covers
SOC
treatment
targeted
therapies
that
shown
to
interfere
different
signaling
pathways
(pRB/CDK4/RB1/P16
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июнь 26, 2024
Glioblastoma
(GBM)
tumors
are
the
most
aggressive
primary
brain
in
adults
that,
despite
maximum
treatment,
carry
a
dismal
prognosis.
GBM
exhibit
tissue
hypoxia,
which
promotes
tumor
aggressiveness
and
maintenance
of
glioma
stem
cells
creates
an
overall
immunosuppressive
landscape.
This
article
reviews
how
hypoxic
conditions
overlap
with
inflammatory
responses,
favoring
proliferation
inhibiting
cytotoxic
T
cell
development.
Immunotherapies,
including
vaccines,
immune
checkpoint
inhibitors,
CAR-T
therapy,
represent
promising
avenues
for
treatment.
However,
challenges
such
as
heterogeneity,
TME,
BBB
restrictiveness
hinder
their
effectiveness.
Strategies
to
address
these
challenges,
combination
therapies
targeting
actively
being
explored
improve
outcomes
patients.
Targeting
hypoxia
immunotherapy
represents
potential
strategy
enhance
treatment
efficacy.
Genes & Development,
Год журнала:
2024,
Номер
unknown
Опубликована: Май 29, 2024
Glioblastoma
(GBM)
is
the
most
aggressive
primary
brain
cancer.
These
tumors
exhibit
high
intertumoral
and
intratumoral
heterogeneity
in
neoplastic
nonneoplastic
compartments,
low
lymphocyte
infiltration,
abundance
of
myeloid
subsets
that
together
create
a
highly
protumorigenic
immunosuppressive
microenvironment.
Moreover,
heterogeneous
GBM
cells
infiltrate
adjacent
tissue,
remodeling
neural
microenvironment
to
foster
tumor
electrochemical
coupling
with
neurons
metabolic
astrocytes,
thereby
driving
growth.
Here,
we
review
its
role
low-to-high-grade
glioma
transition,
concluding
discussion
challenges
therapeutically
targeting
outlining
future
research
opportunities.
Bioengineering & Translational Medicine,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 16, 2025
Abstract
Malignant
brain
tumors,
particularly
glioblastoma
multiforme
(GBM),
are
aggressive
and
fatal
cancers.
The
clinical
efficacy
of
current
standard‐of‐care
treatments
against
tumors
has
been
minimal,
with
no
significant
improvement
over
the
past
30
years.
Driven
by
success
chimeric
antigen
receptor
(CAR)‐T
cells
in
clinic
for
treating
certain
types
cancer,
adoptive
cell
therapies
have
interest
as
a
hopeful
therapeutic
modality
tumors.
Clinical
trials
GBM‐targeting
therapies,
including
CAR‐T
cells,
initiated;
however,
none
them
approved
yet,
new
challenges
emerged
from
completed
trials.
These
issues
being
addressed
ongoing
recent
preclinical
research
efforts.
Herein,
we
present
an
overview
landscape
We
analyze
active
203
focusing
on
discuss
limitations
their
translation,
highlight
emerging
approaches
to
address
these
challenges.
In
addition,
review
select
studies
that
show
promise
improve
future
prospects.
Frontiers in Oncology,
Год журнала:
2025,
Номер
15
Опубликована: Апрель 25, 2025
Background
Tumor
displays
various
forms
of
tumor
heterogeneity
including
immune
that
allow
cancer
cells
to
survive
during
conventional
anticancer
drug
interventions.
Thus,
there
is
a
strong
rationale
for
overcoming
resistance
by
employing
the
components
cells.
Using
system
target
has
revolutionized
treatment.
Recently,
significant
progress
been
achieved
at
preclinical
and
clinical
levels
benefit
patients.
Approach
A
review
literature
from
past
ten
years
across
PubMed,
Scopus,
Web
Science
focused
on
immunotherapy
strategies.
These
include
checkpoint
inhibitors
(ICIs),
tumor-infiltrating
lymphocyte
therapy,
antibody-drug
conjugates
(ADCs),
vaccines,
CAR
T-cell
role
gut
microbiome.
Conclusion
While
outcomes
have
improved,
particularly
types
such
as
melanoma
non-small
cell
lung
(NSCLC),
challenges
persist
regarding
predictive
biomarker
identification
better
management.
Ongoing
research
modifiers
function
like
microbiome-derived
metabolites,
next-generation
ADCs,
new
classes
biologics
warranted.
Overall,
continued
investigation
toward
optimizing
synergistic
immunotherapeutic
combinations
through
strategic
delivery
systems
imperative
success
in
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Апрель 11, 2024
Background
Glioma
is
the
most
common
cancer
of
central
nervous
system
with
poor
therapeutic
response
and
clinical
prognosis.
Insulin-like
growth
factor
1
receptor
(
IGF-1R
)
signaling
implicated
in
tumor
development
progression
induces
apoptosis
cells
following
functional
inhibition.
However,
relationship
between
-related
pathway
genes
glioma
prognosis
or
immunotherapy/chemotherapy
poorly
understood.
Methods
LASSO–Cox
regression
was
employed
to
develop
a
16-gene
risk
signature
TCGA-GBMLGG
cohort,
all
patients
were
divided
into
low-risk
high-risk
subgroups.
The
relationships
immune
microenvironment
(TIME),
immunotherapy
response,
chemotherapy
then
analyzed.
Immunohistochemistry
used
evaluate
HSP90B1
level
tissue.
Results
gene
yielded
superior
predictive
efficacy
(5-year
area
under
curve:
0.875)
can
therefore
serve
as
an
independent
prognostic
indicator
glioma.
subgroup
exhibited
abundant
infltration
elevated
checkpoint
expression
within
TIME.
Subsequent
analysis
revealed
that
benefited
more
from
chemotherapy.
Immunohistochemical
confirmed
overexpressed
glioma,
significantly
higher
levels
observed
glioblastoma
than
astrocytoma
oligodendrocytoma.
Conclusion
newly
identified
demonstrates
robust
capacity
for
plays
pivotal
role
TIME,
thereby
offering
valuable
insights
exploration
novel
biomarkers
targeted
therapeutics.
