Various
cellular
sources
hamper
interpretation
of
positron
emission
tomography
(PET)
biomarkers
in
the
tumor
microenvironment
(TME).
We
developed
an
approach
immunomagnetic
cell
sorting
after
vivo
radiotracer
injection
(scRadiotracing)
with
three-dimensional
(3D)
histology
to
dissect
allocation
PET
signals
TME.
In
mice
implanted
glioblastoma,
translocator
protein
(TSPO)
uptake
per
was
higher
compared
tumor-associated
microglia/macrophages
(TAMs),
validated
by
levels.
Translation
vitro
scRadiotracing
patients
glioma
immediately
resection
confirmed
single-cell
TSPO
tracer
cells
immune
cells.
Across
species,
explained
heterogeneity
individual
TSPO-PET
signals.
consideration
and
type
abundance,
were
main
contributor
enrichment
glioblastoma;
however,
proteomics
identified
potential
targets
highly
specific
for
TAMs.
Combining
measures
3D
facilitates
precise
serves
validate
emerging
novel
TAM-specific
radioligands.
Journal of Neuroinflammation,
Год журнала:
2024,
Номер
21(1)
Опубликована: Март 13, 2024
Abstract
Tissue-resident
macrophages
play
an
important
role
in
the
local
maintenance
of
homeostasis
and
immune
surveillance.
In
central
nervous
system
(CNS),
brain
are
anatomically
divided
into
parenchymal
microglia
non-parenchymal
border-associated
(BAMs).
Among
these
cell
populations,
have
been
well-studied
for
their
roles
during
development
as
well
health
disease.
BAMs,
mostly
located
choroid
plexus,
meningeal
perivascular
spaces,
now
gaining
increased
attention
due
to
advancements
multi-omics
technologies
genetic
methodologies.
Research
on
BAMs
over
past
decade
has
focused
ontogeny,
immunophenotypes,
involvement
various
CNS
diseases,
potential
therapeutic
targets.
Unlike
microglia,
display
mixed
origins
distinct
self-renewal
capacity.
believed
regulate
neuroimmune
responses
associated
with
barriers
contribute
immune-mediated
neuropathology.
Notably,
observed
function
diverse
cerebral
pathologies,
including
Alzheimer’s
disease,
Parkinson’s
multiple
sclerosis,
ischemic
stroke,
gliomas.
The
elucidation
heterogeneity
functions
neuroinflammation
is
mesmerizing,
since
it
may
shed
light
precision
medicine
that
emphasizes
deep
insights
programming
cues
unique
microenvironment.
this
review,
we
delve
latest
findings
covering
aspects
like
origins,
capacity,
adaptability,
implications
different
disorders.
Neuro-Oncology,
Год журнала:
2024,
Номер
26(5), С. 826 - 839
Опубликована: Янв. 18, 2024
Abstract
Background
Glioblastomas
(GBMs)
are
central
nervous
system
tumors
that
resist
standard-of-care
interventions
and
even
immune
checkpoint
blockade.
Myeloid
cells
in
the
tumor
microenvironment
can
contribute
to
GBM
progression;
therefore,
emerging
immunotherapeutic
approaches
include
reprogramming
these
achieve
desirable
antitumor
activity.
Triggering
receptor
expressed
on
myeloid
2
(TREM2)
is
a
signaling
regulator
has
been
implicated
variety
of
cancers
neurological
diseases
with
contrasting
functions,
but
its
role
immunopathology
progression
still
under
investigation.
Methods
Our
reverse
translational
investigations
leveraged
single-cell
RNA
sequencing
cytometry
human
gliomas
characterize
TREM2
expression
across
subpopulations.
Using
distinct
murine
glioma
models,
we
examined
Trem2
modulation
cells.
Furthermore,
designed
method
tracking
phagocytosis
vivo
employed
vitro
assays
mechanistically
understand
influence
uptake.
Results
We
discovered
does
not
correlate
immunosuppressive
pathways,
rather
showed
strong
positive
association
canonical
markers
lysozyme
(LYZ)
macrophage
scavenger
(CD163)
gliomas.
While
deficiency
was
found
be
dispensable
for
gliomagenesis,
Trem2+
display
enhanced
uptake
compared
Trem2-
Mechanistically,
demonstrate
mediates
via
Syk
signaling.
Conclusions
These
results
indicate
associated
immunosuppression
Instead,
an
important
may
exploited
as
potential
therapeutic
strategy
brain
tumors.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Ноя. 14, 2023
Tumor-associated
macrophages
(TAMs)
are
integral
to
the
tumor
microenvironment
(TME),
influencing
cancer
progression
significantly.
Attracted
by
cell
signals,
TAMs
exhibit
unparalleled
adaptability,
aligning
with
dynamic
milieu.
Their
roles
span
from
promoting
growth
and
angiogenesis
modulating
metastasis.
While
substantial
research
has
explored
fundamentals
of
TAMs,
comprehending
their
adaptive
behavior,
leveraging
it
for
novel
treatments
remains
challenging.
This
review
delves
into
TAM
polarization,
metabolic
shifts,
complex
orchestration
cytokines
chemokines
determining
functions.
We
highlight
complexities
TAM-targeted
focusing
on
adaptability
potential
variability
in
therapeutic
outcomes.
Moreover,
we
discuss
synergy
integrating
TAM-focused
strategies
established
treatments,
such
as
chemotherapy,
immunotherapy.
Emphasis
is
laid
pioneering
methods
like
reprogramming
immunotherapy
adoption
single-cell
technologies
precision
intervention.
synthesis
seeks
shed
light
TAMs’
multifaceted
cancer,
pinpointing
prospective
pathways
transformative
enhancing
modalities
oncology.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
25(1), С. 16 - 16
Опубликована: Дек. 19, 2023
Microglia
and
macrophages
are
pivotal
to
the
brain’s
innate
immune
response
have
garnered
considerable
attention
in
context
of
glioblastoma
(GBM)
Alzheimer’s
disease
(AD)
research.
This
review
delineates
complex
roles
these
cells
within
neuropathological
landscape,
focusing
on
a
range
signaling
pathways—namely,
NF-κB,
microRNAs
(miRNAs),
TREM2—that
regulate
behavior
tumor-associated
(TAMs)
GBM
disease-associated
microglia
(DAMs)
AD.
These
pathways
critical
processes
neuroinflammation,
angiogenesis,
apoptosis,
which
hallmarks
We
concentrate
multifaceted
regulation
TAMs
by
NF-κB
GBM,
influence
TREM2
DAMs’
responses
amyloid-beta
deposition,
modulation
both
DAMs
GBM-
AD-related
miRNAs.
Incorporating
recent
advancements
molecular
biology,
immunology,
AI
techniques,
through
detailed
exploration
mechanisms,
we
aim
shed
light
their
distinct
overlapping
regulatory
functions
The
culminates
with
discussion
how
insights
into
miRNAs,
may
inform
novel
therapeutic
approaches
targeting
neurodegenerative
neoplastic
conditions.
comparative
analysis
underscores
potential
for
new,
targeted
treatments,
offering
roadmap
future
research
aimed
at
mitigating
progression
diseases.
Abstract
Background
Glioma
is
a
highly
heterogeneous
brain
tumor
categorized
into
World
Health
Organization
(WHO)
grades
1–4
based
on
its
malignancy.
The
suppressive
immune
microenvironment
of
glioma
contributes
significantly
to
unfavourable
patient
outcomes.
However,
the
cellular
composition
and
their
complex
interplays
within
environment
remain
poorly
understood,
reliable
prognostic
markers
elusive.
Therefore,
in-depth
exploration
(TME)
identification
predictive
are
crucial
for
improving
clinical
management
patients.
Results
Our
analysis
single-cell
RNA-sequencing
data
from
samples
unveiled
immunosuppressive
role
tumor-associated
macrophages
(TAMs),
mediated
through
intricate
interactions
with
cells
lymphocytes.
We
also
discovered
heterogeneity
TAMs,
among
which
group
TAMs
named
TAM-SPP1
demonstrated
significant
association
Epidermal
Growth
Factor
Receptor
(
EGFR
)
amplification,
impaired
T
cell
response
survival
Furthermore,
by
leveraging
genomic
transcriptomic
Cancer
Genome
Atlas
(TCGA)
dataset,
two
distinct
molecular
subtypes
different
constitution
status
outcomes
were
identified.
Exploiting
differences
between
these
subtypes,
we
developed
four-gene-based
model.
This
model
displayed
strong
associations
an
elevated
level
could
be
used
predict
anti-tumor
prognosis
in
Conclusion
findings
illuminated
mechanisms
that
shape
gliomas,
providing
novel
insights
potential
therapeutic
targets.
holds
promise
predicting
immunotherapy
assisting
more
precise
risk
stratification
Graphical
abstract
