Immunogenic Cell Death Inducers in Cancer Immunotherapy to Turn Cold Tumors into Hot Tumors
Valeria Lucarini,
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Ombretta Melaiu,
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Paula Gragera
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et al.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(4), P. 1613 - 1613
Published: Feb. 14, 2025
The
combination
of
chemotherapeutic
agents
with
immune
checkpoint
inhibitors
(ICIs)
has
revolutionized
cancer
treatment.
However,
its
success
is
often
limited
by
insufficient
priming
in
certain
tumors,
including
pediatric
malignancies.
In
this
report,
we
explore
clinical
trials
currently
investigating
the
use
immunogenic
cell
death
(ICD)-inducing
chemotherapies
ICIs
for
both
adult
and
cancers.
Given
data
available
focused
on
recent
preclinical
studies
evaluating
efficacy
these
combinations
neuroblastoma
(NB).
Finally,
to
address
gap,
propose
an
innovative
strategy
assess
impact
ICD-inducing
antitumor
responses
NB.
Using
tumor
spheroids
derived
from
a
transgenic
NB
mouse
model,
validated
our
previous
vivo
findings
concerning
how
anthracyclines,
specifically
mitoxantrone
doxorubicin,
significantly
enhance
MHC
class
I
surface
expression,
stimulate
IFNγ
granzyme
B
production
CD8+
T
cells
NK
cells,
promote
recruitment.
Importantly,
anthracyclines
also
upregulated
PD-L1
expression
spheroids.
This
screening
platform
yielded
results
similar
findings,
demonstrating
that
doxorubicin
are
most
potent
immunomodulatory
These
suggest
creation
libraries
ICD
inducers
be
tested
could
reduce
number
vivo,
line
principles
3Rs.
Furthermore,
highlight
potential
chemo-immunotherapy
regimens
counteract
immunosuppressive
microenvironment
NB,
paving
way
improved
therapeutic
strategies
They
provide
compelling
evidence
support
further
investigations
outcomes
children
Language: Английский
Phase I study of safety and efficacy of allogeneic natural killer cell therapy in relapsed/refractory neuroblastomas post autologous hematopoietic stem cell transplantation
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Sept. 9, 2024
Language: Английский
The anti-GD2 monoclonal antibody naxitamab plus GM-CSF for relapsed or refractory high-risk neuroblastoma: a phase 2 clinical trial
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: Feb. 14, 2025
Abstract
In
this
single-arm,
non-randomized,
phase
2
trial
(NCT03363373),
74
patients
with
relapsed/refractory
high-risk
neuroblastoma
and
residual
disease
in
bone/bone
marrow
(BM)
received
naxitamab
on
Days
1,
3,
5
(3
mg/kg/day)
granulocyte-macrophage
colony-stimulating
factor
(Days
-4
to
5)
every
4
weeks,
until
complete
response
(CR)
or
partial
(PR)
followed
by
additional
cycles
weeks.
Primary
endpoint
the
prespecified
interim
analysis
was
overall
(2017
International
Neuroblastoma
Response
Criteria).
Among
26
responders
(CR
+
PR)
efficacy
population
(
N
=
52),
58%
had
refractory
disease,
42%
relapsed
disease.
Overall
rate
(ORR)
50%
(95%
CI:
36-64%),
CR
PR
were
observed
38%
12%,
respectively.
With
95%
CI
lower
limit
for
ORR
exceeding
20%,
primary
of
met.
Patients
evaluable
bone
a
(29/50)
compartment
(CR,
40%;
PR,
18%).
BM
74%
(17/23;
CR,
74%).
One-year
survival
progression-free
(secondary
endpoints)
93%
80-98%)
35%
16-54%),
Naxitamab-related
Grade
3
adverse
events
included
hypotension
(58%)
pain
(54%).
Overall,
demonstrated
clinically
meaningful
manageable
safety
bone/BM.
Language: Английский
PHD-2/HIF-1α axis mediates doxorubicin-induced angiogenesis in SH-SY5Y neuroblastoma microenvironment: a potential survival mechanism
Ahmed M. Abou‐Shanab,
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Ola A. Gaser,
No information about this author
Noha Galal
No information about this author
et al.
Scientific Reports,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: March 3, 2025
Abstract
The
response
of
neuroblastoma
(NB)
cells
to
chemotherapeutics
and
their
influence
on
NB
microenvironment
remain
incompletely
understood.
Herein,
we
examined
the
underlying
molecular
mechanism
via
which
Doxorubicin,
a
chemotherapeutic
agent
used
for
treatment,
promotes
proangiogenic
in
SH-SY5Y
microenvironment.
Doxorubicin
treatment
at
1
µg/ml
reduced
cell
proliferation
primed
apoptosis
pathway.
Unexpectedly,
treated
with
doxorubicin
upregulated
expression
pro-angiogenic
factors,
including
vascular
endothelial
growth
factor
(VEGF),
platelets-derived
(PDGF),
matrix
metalloprotease-2
(MMP-2)
secretion
nitric
oxide.
To
assess
functional
angiogenesis
pre-treated
doxorubicin,
an
indirect
co-culture
system
human
umbilical
vein
(HUVEC)
was
established.
These
HUVECs
acquired
enhanced
proliferation,
migration
capacity,
tube
formation
capability
exhibited
increased
oxide
(NO)
production,
addition
α-smooth
muscle
actin
expression,
suggesting
contractility.
In-ovo
studies
neo-angiogenic
further
show
promoted
neo-angiogenesis
as
indicated
by
generated
blood
vessels
histological
analysis
CD31
expression.
Inhibition
PHD-2
could
be
potential
target
docking,
dynamics
(MD)
simulation,
MM-GBSA
calculations,
leading
hypoxia-inducible
factor-1
alpha
(HIF-1α)
stabilization.
Bioinformatics
analyses
enrichment
RNA-seq
data
revealed
activation
Pi3K
pathway
is
validated
in-vitro.
results
provide
evidence
unexpected
suggest
use
multi-modal
therapeutic
regimens
more
comprehensive
approach
treatment.
Language: Английский
Longitudinal single-cell multiomic atlas of high-risk neuroblastoma reveals chemotherapy-induced tumor microenvironment rewiring
Wenbao Yu,
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Rumeysa Biyik‐Sit,
No information about this author
Yasin Uzun
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et al.
Nature Genetics,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 14, 2025
Abstract
High-risk
neuroblastoma,
a
leading
cause
of
pediatric
cancer
mortality,
exhibits
substantial
intratumoral
heterogeneity,
contributing
to
therapeutic
resistance.
To
understand
tumor
microenvironment
evolution
during
therapy,
we
longitudinally
profiled
22
patients
with
high-risk
neuroblastoma
before
and
after
induction
chemotherapy
using
single-nucleus
RNA
ATAC
sequencing
whole-genome
sequencing.
This
revealed
profound
shifts
in
immune
cell
subpopulations
therapy
identified
enhancer-driven
transcriptional
regulators
neoplastic
states.
Poor
outcome
correlated
proliferative
metabolically
active
states,
whereas
more
differentiated
neuronal-like
states
predicted
better
prognosis.
Proportions
mesenchymal
cells
increased
high
proportion
poorer
response.
Macrophages
significantly
expanded
towards
pro-angiogenic,
immunosuppressive
metabolic
phenotypes.
We
paracrine
signaling
networks
validated
the
HB-EGF–ERBB4
axis
between
macrophage
subsets,
which
promoted
growth
through
ERK
signaling.
These
findings
collectively
reveal
intrinsic
extrinsic
response
neuroblastoma.
Language: Английский
Hallmarks of Neuroblastoma—Pathophysiology, Diagnosis, and Therapeutic Interventions
Published: May 19, 2025
ABSTRACT
Neuroblastoma,
the
most
common
extracranial
solid
tumor
in
childhood,
continues
to
challenge
clinicians
and
researchers
because
of
its
heterogeneous
nature
complex
pathophysiology.
Recent
breakthroughs
molecular
profiling
revealed
intricate
genetic
alterations
driving
progression,
necessitating
an
updated
perspective
on
disease’s
Rapid
advancements
diagnostic
techniques,
including
novel
imaging
modalities
assays,
warrant
a
thorough
examination
guide
clinical
decision‐making.
Furthermore,
emergence
targeted
therapies
immunotherapeutic
approaches
dramatically
shifted
treatment
landscape,
creating
urgent
need
for
critical
evaluation
their
efficacy
integration
into
existing
protocols.
This
comprehensive
review
is
critically
needed
synthesize
latest
understanding
hallmarks
neuroblastoma,
evolving
therapeutic
approaches.
By
consolidating
current
knowledge
identifying
gaps,
this
aims
provide
valuable
resource
researchers,
potentially
catalyzing
new
research
directions
improving
patient
outcomes.
Language: Английский
Targeting Pathways in Neuroblastoma: Advances in Treatment Strategies and Clinical Outcomes
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(10), P. 4722 - 4722
Published: May 15, 2025
Neuroblastoma
(NB)
is
a
childhood
cancer
originating
from
neural
crest
cells
of
the
sympathetic
nervous
system.
Despite
advances
in
multimodal
therapy,
treatment
high-risk
NB
remains
challenging.
The
present
review
outlines
several
evidence-related
insights
into
molecular
mechanisms
pathogenesis,
focusing
on
genetic
drivers
(e.g.,
MYCN
amplification)
and
disrupted
signaling
pathways
(PI3K/Akt/mTOR;
Notch;
Jak2/STAT3),
as
well
tumor
microenvironment’s
role
progression
resistance.
authors
highlight
current
emerging
therapeutic
strategies,
including
molecularly
targeted
agents;
immunotherapies;
differentiation
approaches
under
investigation.
complexity
heterogeneity
underscores
need
for
continued
translational
research
combined
strategies
aimed
at
improving
outcomes
affected
children,
highlighting
integration
profiling
precision
medicine
to
guide
treatment.
Language: Английский
Exploring the Role of Fibroblasts in Promoting Neuroblastoma Cell Migration and Invasion
Diana Corallo,
No information about this author
C. Nardelli,
No information about this author
Marcella Pantile
No information about this author
et al.
Journal of Nanotheranostics,
Journal Year:
2024,
Volume and Issue:
5(4), P. 212 - 227
Published: Dec. 8, 2024
Neuroblastoma,
the
most
common
pediatric
extracranial
solid
tumor,
arises
from
malignant
transformation
of
neural
crest
progenitors
in
peripheral
nervous
system.
Its
clinical
and
genetic
heterogeneity
poses
significant
challenges,
especially
high-risk
patients
with
metastatic
disease.
Two
plastic
neuroblastoma
cell
phenotypes,
adrenergic
(ADR)
mesenchymal
(MES),
have
been
identified.
Notably,
MES
cells
exhibit
increased
migration
chemoresistance.
Cancer-associated
fibroblasts
(CAFs)
tumor
microenvironment
further
promote
aggressiveness
by
enhancing
cancer
proliferation,
extracellular
matrix
remodeling,
angiogenesis
metastasis.
This
study
explored
role
non-activated
ADR
invasion
vitro
vivo.
Results
showed
that
influenced
fibroblast
activation
into
CAFs
differently,
promoting
a
more
invasive
environment
leading
to
spread.
These
findings
enhance
our
understanding
how
phenotypes
contribute
formation
pro-metastatic
niche
activating
CAFs.
insight
could
inform
new
therapeutic
strategies
targeting
prevent
Language: Английский