Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: May 15, 2025
Natural
killer
(NK)
cells
in
mice
and
humans
are
key
effectors
of
the
innate
immune
system
with
complex
immunoregulatory
functions,
diverse
subsets
have
been
identified
distinct
characteristics
roles.
Companion
dogs
spontaneous
cancer
validated
as
models
human
disease,
including
immunology
immunotherapy,
greater
understanding
NK
cell
heterogeneity
can
inform
biology
across
species
optimize
immunotherapy
for
both
people.
Here,
we
assessed
canine
populations
by
single-cell
RNA
sequencing
(scRNAseq)
blood,
lung,
liver,
spleen,
placenta
comparison
to
from
blood
same
tissues
better
characterize
differential
gene
expression
regarding
ontogeny,
heterogeneity,
patterns
activation,
inhibition,
tissue
residence.
Overall,
observed
tissue-specific
signatures
consistent
immature
placenta,
mature
activated
a
mixed
inhibited
signature
liver
significant
cross-species
homology.
Together,
our
results
point
heterogeneous
highly
comparable
cells,
provide
comprehensive
atlas
organs
which
will
future
studies
further
substantiate
model
species.
Neuro-Oncology,
Journal Year:
2024,
Volume and Issue:
26(12), P. 2174 - 2192
Published: Aug. 5, 2024
Neuroblastoma
(NB),
a
heterogenous
pediatric
tumor
of
the
sympathetic
nervous
system,
is
most
common
and
deadly
extracranial
solid
malignancy
diagnosed
in
infants.
Numerous
efforts
have
been
invested
understanding
its
origin
development
novel
curative
targeted
therapies.
Here,
we
summarize
recent
advances
identification
cell
genetic
alterations
occurring
during
that
contribute
to
NB.
We
discuss
current
treatment
regimens,
present
future
directions
for
therapeutic
metabolic
targets,
differentiation
agents,
as
well
personalized
combinatory
therapies
potential
approaches
improving
survival
quality
life
children
with
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: Feb. 28, 2025
Neuroblastoma
(NB)
is
an
immunologically
“cold”
tumor
with
poor
or
no
inflamed
substrates
as
most
of
solid
pediatric
tumors
(SPT).
Consistent
data
indicate
that
NB
microenvironment
(TME)
dominated
by
myeloid
cells,
little
(but
variable)
T
cell
infiltration.
The
obstacles
to
lymphocyte
infiltration
and
their
anti-tumor
activity
are
due
different
immune
evasion
strategies,
including
loss
HLA
Class
I
molecules,
high
expression
checkpoint
molecular
ligands
leading
exhaustion
effector
(and
NK)
induction
regulatory,
stromal
cells
secretion
immunosuppressive
mediators.
In
odds
adult
tumors,
displays
weak
immunogenicity
caused
intrinsic
low
mutational
burden
scant
neoepitopes
in
the
context
MHC-class
antigens
which,
turn,
particularly
poorly
expressed
on
thus
inducing
responses.
addition,
generated
from
embryonal
result
transcriptional
abnormalities
not
accumulation
genetic
mutations
over
time,
further
explaining
immunogenicity.
immunogenic
molecules
associated
production
factors
which
downregulate
activity,
limited
efficacy
new
drugs
NB,
inhibitors.
This
review
focused
examining
role
regulatory
infiltrating
TME
taking
into
account
repertoire,
phenotype,
function,
plasticity
and,
importantly,
predictive
value
for
defining
novel
targets
therapy.
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.
ABSTRACT
Cancer
research
predominantly
centers
on
diagnosis,
treatment,
and
elucidation
of
underlying
mechanisms.
Nevertheless,
the
intricate
nature
tumor
genesis
development
has
rendered
early
diagnostic
therapeutic
outcomes
less
than
optimal,
making
conquest
a
formidable
challenge.
The
interdisciplinary
fusion
medicine
engineering,
termed
“intersection
engineering”,
emerged
as
groundbreaking
paradigm,
offering
novel
avenues
for
advancing
cancer
studies.
As
this
approach
evolves,
it
yielded
numerous
breakthroughs
in
mechanistic
exploration.
In
review,
we
summarize
how
intersection
engineering
propels
progress
by
leveraging
combined
strengths
medicine,
bioinformatics,
materials
science,
artificial
intelligence.
This
addresses
limitations
traditional
diagnostics
therapies,
such
low
sensitivity,
poor
efficacy,
significant
side
effects,
challenges
associated
with
Moreover,
highlight
global
cutting‐edge
advancements
potential
future
directions
field.