European Heart Journal,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 19, 2025
Abstract
Backgrounds
and
Aims
Patients
with
periodontitis
(PD)
are
prone
to
developing
myocardial
infarction
(MI),
yet
the
prognosis
mechanisms
remain
unclear.
Given
presumed
close
association
of
neutrophils
both
conditions,
this
study
aims
elucidate
roles
in
mediating
interaction
between
PD
MI.
Methods
Three
prospective
cohorts
+
MI
mouse
model
were
investigated
assess
effects
on
prognosis.
Single-cell-RNA
sequencing
genome-wide
employed
identify
neutrophil
subtype
involved.
To
characterize
function
SiglecF+
neutrophils,
bone
marrow
transplantation,
Edu-pulse
chasing,
lineage
tracing,
collagen
contraction
assay
utilized.
Adoptive
transfer,
conditional
Siglecf
knockout
lipid
nanoparticles
facilitating
local
depletion
was
harnessed
explore
repair.
Results
Persisting
but
not
short-term
upset
(cardiac
fibrosis
function)
human
mice.
Bone
intrinsically
skewed
toward
longer-lived
differentiation,
a
that
converted
by
GMCSF
or
TGFβ
PPARγ-dependent
manner.
expanded
infarcted
heart
where
they
deposit
activate
fibroblasts
instigate
excessive
fibrosis.
efficacious
for
mitigating
Conclusions
This
demonstrated
long-lasting
PD-aggravated
expanding
scar-associated
into
highlighted
clinical
relevance
oral
health
examination
treating
holistic
fashion.
Journal of Hematology & Oncology,
Journal Year:
2024,
Volume and Issue:
17(1)
Published: June 4, 2024
Abstract
Pancreatic
cancer
is
a
major
cause
of
cancer-related
death,
but
despondently,
the
outlook
and
prognosis
for
this
resistant
type
tumor
have
remained
grim
long
time.
Currently,
it
extremely
challenging
to
prevent
or
detect
early
enough
effective
treatment
because
patients
rarely
exhibit
symptoms
there
are
no
reliable
indicators
detection.
Most
advanced
spreading
that
difficult
treat,
treatments
like
chemotherapy
radiotherapy
can
only
slightly
prolong
their
life
by
few
months.
Immunotherapy
has
revolutionized
pancreatic
cancer,
yet
its
effectiveness
limited
tumor's
immunosuppressive
hard-to-reach
microenvironment.
First,
article
explains
microenvironment
highlights
wide
range
immunotherapy
options,
including
therapies
involving
oncolytic
viruses,
modified
T
cells
(T-cell
receptor
[TCR]-engineered
chimeric
antigen
[CAR]
T-cell
therapy),
CAR
natural
killer
cell
therapy,
cytokine-induced
cells,
immune
checkpoint
inhibitors,
immunomodulators,
vaccines,
strategies
targeting
myeloid
in
context
contemporary
knowledge
future
trends.
Lastly,
discusses
main
challenges
ahead
immunotherapy.
Journal for ImmunoTherapy of Cancer,
Journal Year:
2025,
Volume and Issue:
13(1), P. e010212 - e010212
Published: Jan. 1, 2025
Fibroblast
activation
protein
(FAP)-targeted
radioligand
therapy,
with
immunomodulatory
effects,
has
shown
efficacy
in
both
preclinical
and
clinical
studies.
We
recently
reported
on
a
novel
dimeric
FAP-targeting
radiopharmaceutical,
68Ga/177Lu-DOTA-2P(FAPI)2,
which
demonstrated
increased
tumor
uptake
prolonged
retention
various
cancers.
However,
further
exploration
is
required
to
understand
the
therapeutic
underlying
mechanisms
of
combining
68Ga/177Lu-DOTA-2P(FAPI)2
therapy
PD-1/PD-L1
immunotherapy.
Regarding
change
PD-L1
expression
DNA
double-strand
breaks
induced
by
radiopharmaceuticals,
CT26-FAP
cells
were
incubated
68Ga
177Lu
labeled
DOTA-2P(FAPI)2,
respectively.
Monotherapy
68Ga-DOTA-2P(FAPI)2,
177Lu-DOTA-2P(FAPI)2,
immunotherapy
as
well
combination
(68Ga/177Lu-DOTA-2P(FAPI)2
immunotherapy)
tested
evaluated
evaluate
vivo
antitumor
efficacy.
Furthermore,
immunohistochemical
staining
single-cell
RNA
sequencing
used
analyze
changes
microenvironment
(TME)
elucidate
action
this
therapy.
Our
findings
indicated
that
radiopharmaceuticals
can
induce
upregulate
expression,
177Lu-DOTA-2P(FAPI)2
proving
be
more
effective
than
68Ga-DOTA-2P(FAPI)2.
Both
68Ga-DOTA-2P(FAPI)2
significantly
improved
outcomes
when
combined
anti-PD-L1
monoclonal
antibody
(αPD-L1
mAb).
Notably,
αPD-L1
mAb
eliminated
tumors
mouse
models.
Mice
treated
regimen
not
only
exhibited
exceptional
responses
initial
immune
checkpoint
inhibitor
but
also
showed
100%
rejection
subsequent
cell
re-inoculation.
Further
mechanistic
studies
have
reprogram
TME,
enhancing
intercellular
communication,
activates
antitumor-related
contacts
such
FasL-Fas
interactions
between
T
NK
increasing
proportion
infiltrating
CD8+
T-cells
while
reducing
regulatory
inhibiting
progression.
research
demonstrates
mature
neutrophils
play
role
neutrophil-blocking
experiments.
study
robustly
advocates
for
use
particularly
alongside
treating
FAP-positive
tumors.
This
transforms
TME
enables
translatable
approach
sensitivity
immunotherapy,
leading
complete
remission
rates
extended
overall
survival.
MedComm,
Journal Year:
2025,
Volume and Issue:
6(2)
Published: Jan. 21, 2025
Abstract
Neutrophils,
the
most
abundant
circulating
leukocytes,
have
long
been
recognized
as
key
players
in
innate
immunity
and
inflammation.
However,
recent
discoveries
unveil
their
remarkable
heterogeneity
plasticity,
challenging
traditional
view
of
neutrophils
a
homogeneous
population
with
limited
functional
repertoire.
Advances
single‐cell
technologies
assays
revealed
distinct
neutrophil
subsets
diverse
phenotypes
functions
ability
to
adapt
microenvironmental
cues.
This
review
provides
comprehensive
overview
multidimensional
landscape
heterogeneity,
discussing
various
axes
along
which
diversity
manifests,
including
maturation
state,
density,
surface
marker
expression,
polarization.
We
highlight
molecular
mechanisms
underpinning
focusing
on
complex
interplay
signaling
pathways,
transcriptional
regulators,
epigenetic
modifications
that
shape
responses.
Furthermore,
we
explore
implications
plasticity
physiological
processes
pathological
conditions,
host
defense,
inflammation,
tissue
repair,
cancer.
By
integrating
insights
from
cutting‐edge
research,
this
aims
provide
framework
for
understanding
multifaceted
roles
potential
therapeutic
targets
wide
range
diseases.
