Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Май 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.
Journal of Clinical Medicine,
Год журнала:
2025,
Номер
14(2), С. 527 - 527
Опубликована: Янв. 15, 2025
Background/Objectives:
Neuroblastoma
is
a
highly
aggressive
pediatric
cancer
that
arises
from
immature
nerve
cells
and
exhibits
broad
spectrum
of
clinical
presentations.
While
low-
intermediate-risk
neuroblastomas
often
have
favorable
outcomes,
high-risk
are
associated
with
poor
prognosis
significant
treatment
challenges.
The
complex
genetic
networks
driving
these
cases
remain
poorly
understood.
This
study
aims
to
investigate
differences
in
gene
expression
patterns
may
contribute
disease
outcomes.
Methods:
We
employed
an
silico
approach
analyze
cohort
493
neuroblastoma
tumor
samples
underwent
mRNA
sequencing
(GSE49711).
dataset
was
reanalyzed
depth
non-hypothesis-driven
identify
the
regulatory
mechanisms
prognosis.
Results:
By
exploring
global
integration
parameters,
we
stratified
into
two
groups
distinct
profiles.
MYCN
amplification
emerged
as
major
driver
not
only
but
also
specific
patterns.
Notably,
tumors
exhibited
strong
regulation
immune
response
genes
less
infiltration,
suggesting
potential
evasion.
However,
while
observed
minor
changes
checkpoint
expression,
there
modulation
glycosyltransferase
MYCN-amplified
tumors.
Using
this
information,
were
able
construct
risk
profile
based
on
12
glycosylation-related
genes,
which
correlates
survival
outcomes
patients.
Conclusions:
highlights
role
through
genes.
Based
finding,
developed
Frontiers in Oncology,
Год журнала:
2025,
Номер
15
Опубликована: Март 4, 2025
Neuroblastoma
is
a
pediatric
cancer
that
originates
from
neural
crest
cells
and
the
most
common
extracranial
solid
tumor
in
children
under
five
years
of
age.
While
low-risk
neuroblastoma
often
regresses
spontaneously,
high-risk
poses
significant
clinical
challenge.
Recent
advances
understanding
neuroblastoma’s
molecular
mechanisms
have
led
to
development
targeted
therapies
aim
selectively
inhibit
specific
pathways
involved
growth
progression,
improving
patient
outcomes
while
minimizing
side
effects.
This
review
provides
comprehensive
biology
emerging
therapeutic
strategies.
Key
topics
include
(a)
immunotherapies
immunotargets,
(b)
non-coding
RNAs
(long
RNA,
microRNA,
circular
RNA),
(c)
biomarkers
pathways,
(d)
limitations
future
directions.
Journal for ImmunoTherapy of Cancer,
Год журнала:
2024,
Номер
12(5), С. e008983 - e008983
Опубликована: Май 1, 2024
The
incidence
of
papillary
thyroid
cancer
(PTC)
continues
to
rise
all
over
the
world,
10-15%
patients
have
a
poor
prognosis.
Although
immunotherapy
has
been
applied
in
clinical
practice,
its
therapeutic
efficacy
remains
far
from
satisfactory,
necessitating
further
investigation
mechanism
PTC
immune
remodeling
and
exploration
novel
treatment
targets.
This
study
conducted
single-cell
RNA
sequencing
(scRNA-seq)
analysis
using
18
surgical
tissue
specimens
procured
14
diagnosed
with
adjacent
tissues,
non-progressive
or
progressive
PTC.
Key
findings
were
authenticated
through
spatial
transcriptomics
sequencing,
immunohistochemistry,
multiplex
an
independent
bulk
RNA-seq
data
set
containing
502
samples.
A
total
151,238
individual
cells
derived
underwent
scRNA-seq
analysis.
We
found
that
exhibits
following
characteristics:
significant
decrease
overall
cells,
enhanced
evasion
tumor
disrupted
antigen
presentation
function.
Moreover,
we
identified
subpopulation
lysosomal
associated
membrane
protein
3
(LAMP3+)
dendritic
(DCs)
exhibiting
heightened
infiltration
advanced
T
stage
prognosis
LAMP3+
DCs
promote
CD8+
exhaustion
(mediated
by
NECTIN2-TIGIT)
increase
abundance
regulatory
chemokine
(C-C
motif)
ligand
17
(CCL17)-chemokine
receptor
4
(CCR4))
establishing
immune-suppressive
microenvironment.
Ultimately,
unveiled
facilitate
retention
within
microenvironment
NECTIN3-NECTIN2
interactions,
thereby
rendering
more
susceptible
evasion.
Our
expound
valuable
insights
into
role
interaction
between
T-cell
subpopulations
offer
new
effective
ideas
strategies
for
EJC Paediatric Oncology,
Год журнала:
2024,
Номер
3, С. 100161 - 100161
Опубликована: Апрель 7, 2024
Neuroblastoma
is
a
cancer
of
the
sympathetic
nervous
system
that
develops
in
young
children,
either
as
low-risk
or
high-risk
disease.
The
tumor
microenvironment
(TME)
now
recognized
an
important
player
ecosystem
may
promote
drug
resistance
and
immune
escape.
Targeting
TME
combination
with
therapies
directly
targeting
cells
therefore
represents
interesting
strategy
to
prevent
emergence
improve
patient's
outcome.
development
such
strategies
however
requires
in-depth
understanding
landscape,
due
its
high
complexity
intra
inter-tumoral
heterogeneity.
Various
approaches
have
been
used
last
years
characterize
non-immune
cell
populations
present
tumors
neuroblastoma
patients,
both
quantitatively
qualitatively,
particular
use
single-cell
transcriptomics.
It
anticipated
near
future,
genomic
information
will
contribute
precise
approach
therapy
neuroblastoma.Deciphering
mechanisms
interaction
between
stromal
key
identify
novel
therapeutic
combinations.
Over
decade,
numerous
vitro
studies
vivo
pre-clinical
experiments
immune-competent
immune-deficient
models
identified
circumvent
Some
these
formed
basis
for
early
phase
I
II
clinical
trials
children
recurrent
refractory
neuroblastoma.
This
review
summarizes
recently
published
data
on
characterization
landscape
various
cellular
components,
molecules
pathways
activated
result
tumor-host
interactions.
Cancer Discovery,
Год журнала:
2024,
Номер
unknown, С. OF1 - OF20
Опубликована: Июль 31, 2024
Abstract
Relapse
rates
in
high-risk
neuroblastoma
remain
exceedingly
high.
The
malignant
cells
that
are
responsible
for
relapse
have
not
been
identified,
and
mechanisms
of
therapy
resistance
poorly
understood.
In
this
study,
we
used
single-nucleus
RNA
sequencing
bulk
whole-genome
to
identify
characterize
the
residual
persister
survive
chemotherapy
from
a
cohort
20
matched
diagnosis
definitive
surgery
tumor
samples
patients
treated
with
induction
chemotherapy.
We
show
share
common
escape,
including
suppression
MYC(N)
activity
activation
NFκB
signaling,
latter
is
further
enhanced
by
cell–cell
communication
between
microenvironment.
Overall,
our
work
dissects
transcriptional
landscape
cellular
persistence
paves
way
development
new
therapeutic
strategies
prevent
disease
relapse.
Significance:
Approximately
50%
die
relapsed
refractory
disease.
identified
likely
contribute
discovered
key
signaling
pathways
mediate
persistence.
Inhibition
these
their
downstream
effectors
postulated
eliminate
Cell Genomics,
Год журнала:
2025,
Номер
5(1), С. 100739 - 100739
Опубликована: Янв. 1, 2025
Exploratory
analysis
of
single-cell
RNA
sequencing
(scRNA-seq)
typically
relies
on
hard
clustering
over
two-dimensional
projections
like
uniform
manifold
approximation
and
projection
(UMAP).
However,
such
methods
can
severely
distort
the
data
have
many
arbitrary
parameter
choices.
Methods
that
model
scRNA-seq
as
non-discrete
"gene
expression
programs"
(GEPs)
better
preserve
data's
structure,
but
currently,
they
are
often
not
scalable,
consistent
across
repeated
runs,
lack
an
established
method
for
choosing
key
parameters.
Here,
we
developed
a
GPU-based
unsupervised
learning
approach,
"consensus
scalable
inference
gene
(CSI-GEP).
We
show
CSI-GEP
recover
ground
truth
GEPs
in
real
simulated
atlas-scale
datasets,
significantly
outperforming
cutting-edge
methods,
including
GPT-based
neural
networks.
applied
to
whole
mouse
brain
atlas
2.2
million
cells,
disentangling
endothelial
cell
types
missed
by
other
integrated
human
tumors
lines,
discovering
mesenchymal-like
unique
cancer
cells
growing
culture.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Авг. 21, 2024
Novel
chimeric
antigen
receptor
(CAR)
T-cell
approaches
are
needed
to
improve
therapeutic
efficacy
in
solid
tumors.
High-risk
neuroblastoma
is
an
aggressive
pediatric
tumor
that
expresses
cell-surface
GPC2
and
GD2
with
a
microenvironment
infiltrated
by
CD16a-expressing
innate
immune
cells.
Here
we
engineer
T-cells
express
GPC2-directed
CAR
simultaneously
secrete
bispecific
cell
engager
(BiCE)
targeting
both
CD16a.
In
vitro,
GPC2.CAR-GD2.BiCE
induce
GPC2-dependent
cytotoxicity
GD2.BiCE
promotes
GD2-dependent
activation
of
antitumor
immunity.
vivo,
locally
deliver
increase
intratumor
retention
NK-cells.
mice
bearing
patient-derived
xenografts
reconstituted
human
cells,
GD2.BiCEs
enhance
GPC2.CAR
efficacy.
A
CAR.BiCE
strategy
should
be
considered
for
histologies
where
escape
limits
efficacy,
especially
tumors
like
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 20, 2024
To
uncover
the
intricate,
chemotherapy-induced
spatiotemporal
remodeling
of
tumor
microenvironment,
we
conducted
integrative
spatial
and
molecular
characterization
97
high-grade
serous
ovarian
cancer
(HGSC)
samples
collected
before
after
chemotherapy.
Using
single-cell
analyses,
identify
increasingly
versatile
immune
cell
states,
which
form
spatiotemporally
dynamic
microcommunities
at
tumor-stroma
interface.
We
demonstrate
that
chemotherapy
triggers
redistribution
exhaustion
CD8+
T
cells
due
to
prolonged
antigen
presentation
by
macrophages,
both
within
interconnected
myeloid
networks
termed
"Myelonets"
stroma
Single-cell
transcriptomics
identifies
prominent
TIGIT-NECTIN2
ligand-receptor
interactions
induced
a
functional
patient-derived
immuno-oncology
platform,
show
CD8+T-cell
activity
can
be
boosted
combining
checkpoint
blockade
with
Our
discovery
myeloid-driven
T-cell
paves
way
for
novel
immunotherapeutic
strategies
unleash
T-cell-mediated
anti-tumor
immunity
in
HGSC.