Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Май 8, 2025
Background
Multiple
myeloma
(MM)
is
a
biologically
heterogeneous
malignancy
of
clonal
plasma
cells,
often
progressing
from
MGUS
or
smoldering
MM.
It
causes
anemia,
bone
lesions,
and
immune
dysfunction
due
to
abnormal
cell
expansion
in
the
marrow.
Neuroinflammatory
neurotrophic
factors
may
influence
MM
progression
by
affecting
cells
marrow
niche.
Growing
evidence
points
role
for
neuroimmune
regulation
tumor
immunity.
Despite
therapeutic
progress,
disease
heterogeneity
resistance
highlight
need
new
strategies
targeting
microenvironment
axis.
Methods
This
investigation
exploited
single-cell
RNA
sequencing
(scRNA-seq)
analyze
high-risk
multiple
(SMMh)
samples,
identifying
11
distinct
types.
We
examined
their
transcriptional
signatures,
stemness,
proliferative
properties,
metabolic
pathways,
with
particular
attention
interactions
microenvironment.
Using
trajectory
inference
tools
such
as
CytoTRACE,
Monocle2,
Slingshot,
we
traced
differentiation
paths
subpopulations
identified
key
signaling
pathways
that
responses
progression.
Results
The
analysis
four
C0
IGLC3+
representing
least
differentiated
most
subset.
These
played
critical
contribute
evasion
mechanisms.
Additionally,
receptor-ligand
within
were
identified,
which
be
influenced
neuroinflammatory
factors.
findings
suggest
nervous
system
modulation
significantly
affect
biology,
highlighting
potential
targets
could
overcome
conventional
therapies.
Conclusion
provided
insights
into
cellular
diversity
trajectories
MM,
offering
deeper
understanding
complex
drive
resistance.
By
incorporating
neuroinflammation
modulation,
our
study
suggested
novel
axis
oncology,
ultimately
contributing
development
more
effective,
personalized
treatment
approaches
Frontiers in Immunology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 7, 2025
Cervical
cancer
is
the
fourth
most
common
in
women
globally,
and
main
cause
of
disease
has
been
found
to
be
ongoing
HPV
infection.
remains
primary
cancer-related
death
despite
major
improvements
screening
treatment
approaches,
especially
low-
middle-income
nations.
Therefore,
it
crucial
investigate
tumor
microenvironment
advanced
cervical
order
identify
possible
targets.
In
better
understand
malignant
epithelial
cells
(EPCs),
this
study
used
bulk
RNA-seq
data
from
UCSC
conjunction
with
single-cell
RNA
sequencing
ArrayExpress
database.
After
putting
quality
control
procedures
into
place,
cell
type
identification
clustering
analysis
using
Seurat
software
were
carried
out.
To
clarify
functional
pathways,
enrichment
differential
gene
expression
The
CIBERSORT
ESTIMATE
R
packages
evaluate
immune
characteristics,
univariate
multivariate
Cox
regression
analyses
extract
prognostic
features.
Furthermore,
assessments
drug
sensitivity
Eight
types
identified,
EPCs
showing
high
proliferative
stemness
Five
EPC
subpopulations
defined,
C1
NNMT+
CAEPCs
driving
differentiation.
A
NNMT
Risk
Score
(NCRS)
model
was
developed,
revealing
a
correlation
between
elevated
NCRS
scores
adverse
patient
outcomes
characterized
by
evasion.
vitro
experiments
validated
that
PLOD2
significantly
enhances
proliferation,
migration,
invasion
cells.
This
investigation
delineated
eight
five
cancer,
establishing
as
therapeutic
target.
demonstrated
its
capability,
indicating
higher
are
associated
poorer
clinical
outcomes.
validation
highlights
potential,
underscoring
critical
need
for
integrating
immunotherapy
targeted
strategies
enhance
diagnostic
approaches
cancer.
Melanoma
is
an
aggressive
type
of
skin
cancer
that
arises
from
melanocytes,
the
cells
responsible
for
producing
pigment.
In
contrast
to
non-melanoma
cancers
like
basal
cell
carcinoma
and
squamous
carcinoma,
melanoma
more
invasive.
was
distinguished
by
its
rapid
progression,
high
metastatic
potential,
significant
resistance
conventional
therapies.
Although
it
accounted
a
small
proportion
cases,
accounts
majority
deaths
caused
due
ability
invade
deep
tissues,
adapt
diverse
microenvironments,
evade
immune
responses.
These
unique
features
highlighted
challenges
treating
underscored
importance
advanced
tools,
such
as
single-cell
sequencing,
unravel
biology
develop
personalized
therapeutic
strategies.
Thus,
we
conducted
analysis
cellular
composition
within
tumor
tissues
further
subdivided
into
subpopulations.
Through
analyzing
metabolic
pathways,
stemness
genes,
transcription
factors
(TFs)
among
in
different
phases
(G1,
G2/M,
S)
well
between
primary
foci
cells,
investigated
specific
mechanisms
underlying
metastasis.
We
also
revisited
temporal
trajectories
subpopulations,
identifying
core
subpopulation
C0
SOD3
+
cells.
Our
findings
revealed
close
relationship
pivotal
oxidative
pathways
tissues.
Additionally,
analyzed
prognostically
relevant
differentially
expressed
genes
(DEGs)
built
predictive
model
associated
with
outcomes.
selected
gene
IGF1
highest
coefficient
(coef)
value
analysis,
experimentally
validated
essential
function
proliferation
invasive
metastasis
melanoma.
infiltration
discovered
critical
roles
played
M1/M2
macrophages
progression
evasion.
Furthermore,
development
malignant
were
closely
various
forms
programmed
death
(PCD),
including
apoptosis,
autophagic
death,
ferroptosis,
pyroptosis.
often
resisted
mechanisms,
maintaining
their
growth
inhibiting
apoptosis
evading
death.
Meanwhile,
induction
ferroptosis
pyroptosis
thought
trigger
responses
helped
suppress
dissemination.
A
deeper
understanding
PCD
provided
foundation
developing
novel
targeted
therapies,
potential
enhance
treatment
efficacy.
contributed
prognostic
models
shed
light
on
research
directions
concerning
targets.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Март 6, 2025
Breast
Cancer
(BC)
ranks
among
the
top
three
most
prevalent
cancers
globally
and
stands
as
principal
contributor
to
cancer-related
fatalities
women.
In
spite
of
substantial
occurrence
rate
BC,
early
stage
this
disease
is
generally
regarded
curable.
However,
intra-tumor
heterogeneity
presents
a
formidable
obstacle
success
effective
treatment.
research,
single
cell
RNA
sequencing
was
utilized
dissect
tumor
microenvironment
within
BC.
Slingshot,
CytoTRACE
Monocle
2
were
applied
illustrate
differentiation
process
each
subpopulation
in
pseudotime
sequence.
To
comprehensively
comprehend
cells
(TCs)
an
analysis
upstream
transcription
factors
carried
out
via
pySCENIC,
while
downstream
pathway
enrichment
conducted
through
KEGG,
GO
GSEA.
The
prognosis
model
established
based
on
bulk
data
obtained
from
TCGA
GEO
databases.
Knock-down
experiments
also
implemented
explore
function
factor
CEBPD
TCs.
Our
in-depth
identified
eight
types.
Notably,
TCs
predominantly
found
epithelial
cells.
classification
further
uncovered
five
unique
subpopulations,
with
one
characterized
by
high
UGDH
expression.
This
shown
possess
distinct
metabolic
features
metabolism-related
investigations.
intricate
communication
modalities
different
types
effectively
demonstrated
means
CellChat.
Additionally,
crucial
factor,
CEBPD,
identified,
which
pronounced
propensity
towards
tumors
harbored
potential
tumor-advancing
characteristics.
Its
role
promoting
cancer
subsequently
verified
vitro
knock-down
experiments.
Moreover,
prognostic
developed,
risk
score
genes
incorporated
model.
Through
comparing
prognoses
UTRS
levels,
it
determined
that
group
had
less
favorable
prognosis.
These
outcomes
contributed
elucidation
complex
interrelationships
BC
microenvironment.
By
specifically
targeting
certain
subpopulations
TCs,
novel
treatment
strategies
could
potentially
be
devised.
study
shed
light
direction
future
research
should
take,
furnishing
valuable
information
can
enhance
regimens.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 9, 2025
Systemic
lupus
erythematosus
(SLE)
is
a
persistent
autoimmune
disorder
marked
by
dysregulation
of
the
immune
system,
resulting
in
extensive
tissue
inflammation
and
subsequent
damage.
Fibroblasts
are
essential
contributors
to
pathogenesis
SLE,
particularly
driving
progression
fibrosis
inflammation.
Recent
research
has
proposed
that
GEM
gene
may
regulate
fibroblast
activity
SLE.
However,
precise
molecular
mechanisms
through
which
modulates
functions
context
SLE
yet
be
fully
elucidated.
Gaining
insight
into
these
crucial
for
uncovering
potential
therapeutic
targets
aimed
at
addressing
associated
with
Single-cell
RNA
sequencing
was
integrated
cell-based
assays,
such
as
quantitative
reverse
transcription
PCR
(qRT-PCR)
functional
cellular
experiments,
investigate
underlying
mechanisms.
The
regulatory
fibroblasts
were
analyzed
cell
assays.
Differential
expression
subpopulations
identified
single-cell
sequencing,
emerging
key
implicated
alterations.
Trajectory
analysis
indicated
correlated
proliferation
migration.
Subsequent
experiments
confirmed
regulates
viability
influences
disease
modulation
proliferation,
migration,
apoptosis.
highly
differentially
expressed
within
its
altered
impacts
apoptosis,
potentially
contributing
Frontiers in Oncology,
Год журнала:
2025,
Номер
15
Опубликована: Апрель 9, 2025
Diffuse
large
B-cell
lymphoma
(DLBCL)
is
a
highly
heterogeneous
malignancy
with
challenges
in
treatment
resistance
and
relapse.
Single-cell
RNA
sequencing
(scRNA-seq)
has
provided
important
insights
into
tumor
heterogeneity,
microenvironment
interactions,
mechanisms,
prognostic
biomarkers.
This
review
summarizes
key
findings
from
scRNA-seq
studies,
which
have
deepened
our
understanding
of
DLBCL
contributed
to
the
development
precision
therapeutic
strategies.
Integrating
spatial
transcriptomics
single-cell
multi-omics
may
further
elucidate
disease
mechanisms
identify
novel
targets,
supporting
advancement
medicine
DLBCL.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 30, 2025
Bladder
cancer
is
a
prevalent
malignancy,
with
muscle-invasive
bladder
(MIBC)
presenting
significant
therapeutic
challenge.
Standard
treatments,
including
radical
cystectomy
(RC)
and
neoadjuvant
chemotherapy,
pose
substantial
risks
impact
quality
of
life,
leading
to
increasing
interest
in
bladder-preserving
therapies
(BPT).
Immunotherapy
has
revolutionized
management,
strategies
ranging
from
intravesical
Bacillus
Calmette-Guérin
(BCG)
immune
checkpoint
inhibitors
targeting
programmed
cell
death
protein
1
(PD-1)
its
ligand
(PD-L1).
In
BCG-unresponsive
non-muscle-invasive
(NMIBC),
PD-1
such
as
pembrolizumab
offer
promising
response
rates.
MIBC,
immunotherapy
agents
like
atezolizumab
improves
pathological
complete
(pCR)
facilitates
preservation.
Combination
regimens
integrating
radiotherapy,
not
only
enhance
treatment
efficacy
but
also
exploit
mechanisms
immunogenic
antigen
release
that
further
augment
antitumor
responses.
This
review
provides
comprehensive
analysis
current
immunotherapeutic
for
invasive
cancer,
highlighting
their
clinical
applications
future
potential.