The Journal of Cell Biology,
Год журнала:
2024,
Номер
224(2)
Опубликована: Ноя. 21, 2024
Macrophages
are
primary
cells
of
the
innate
immune
system
that
mediate
tumor
progression.
However,
motile
behavior
macrophages
and
interactions
with
not
well
understood.
Here,
we
exploit
optical
transparency
larval
zebrafish
perform
real-time
imaging
macrophage–melanoma
interactions.
We
found
highly
in
microenvironment.
extend
dynamic
projections
between
precede
invasive
melanoma
migration.
Modulating
macrophage
motility
a
dominant
inhibitory
mutation
Rac2
inhibits
recruitment
to
impairs
invasion.
hyperactivating
does
affect
but
limits
into
mass
reduces
cell
Taken
together,
these
findings
reveal
role
for
Rac2-mediated
protrusive
Abstract
Approximately
half
of
melanoma
patients
relapse
or
fail
to
respond
current
standards
care,
highlighting
the
need
for
new
treatment
options.
Engineering
T-cells
with
chimeric
antigen
receptors
(CARs)
has
revolutionized
hematological
malignancies
but
been
clinically
less
effective
in
solid
tumors.
We
therefore
sought
engineer
alternative
immune
cell
types
inhibit
progression.
macrophages
CARs
emerged
as
a
promising
approach
overcome
some
challenges
faced
by
CAR-T
cells;
however,
whether
these
engineered
can
effectively
growth
is
unknown.
To
determine
CAR-macrophages
(CAR-Ms)
specifically
target
and
kill
cells,
we
CAR-Ms
targeting
chondroitin
sulfate
proteoglycan
4
(CSPG4),
an
expressed
melanoma.
CSPG4-targeting
exhibited
specific
phagocytosis
CSPG4-expressing
cells.
developed
3D
approaches
show
that
efficiently
infiltrated
spheroids.
Furthermore,
combining
strategies
inhibiting
CD47/SIRPα
“don’t
eat
me”
signaling
synergistically
enhanced
CAR-M-mediated
robustly
inhibited
spheroid
3D.
Importantly,
tumor
mouse
models.
These
results
suggest
engineering
against
antigens
immunotherapy
treating
Science Immunology,
Год журнала:
2024,
Номер
9(96)
Опубликована: Июнь 7, 2024
Professional
phagocytes
like
neutrophils
and
macrophages
tightly
control
what
they
consume,
how
much
when
move
after
cargo
uptake.
We
show
that
plasma
membrane
abundance
is
a
key
arbiter
of
these
cellular
behaviors.
Neutrophils
lacking
the
G
protein
subunit
Gβ
Proceedings of the National Academy of Sciences,
Год журнала:
2023,
Номер
120(52)
Опубликована: Дек. 18, 2023
The
21kD
GTPase
Rac
is
an
evolutionarily
ancient
regulator
of
cell
shape
and
behavior.
Rac2
predominantly
expressed
in
hematopoietic
cells
where
it
essential
for
survival
motility.
hyperactivating
mutation
E62K
also
causes
human
immunodeficiency,
although
the
mechanism
remains
unexplained.
Here,
we
report
that
Drosophila,
stimulates
ovarian
to
cannibalize
neighboring
cells,
destroying
tissue.
We
then
show
hyperactive
HL60-derived
macrophage-like
engulf
kill
living
T
leukemia
cells.
Primary
mouse
+/E62K
bone-marrow-derived
macrophages
primary
due
a
combination
macrophage
hyperactivity
hypersensitivity
engulfment.
Additionally,
non-autonomously
stimulate
wild-type
enhances
engulfment
target
cancer
by
chimeric
antigen
receptor-expressing
(CAR-M)
CAR-dependent
manner.
propose
Rac-mediated
cannibalism
may
contribute
immunodeficiency
enhance
CAR-M
immunotherapy.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 8, 2025
Abstract
Macrophage
phagocytosis
is
an
essential
immune
response
that
eliminates
pathogens,
antibody-opsonized
cancer
cells
and
debris.
Macrophages
can
also
trogocytose,
or
nibble,
targets.
Trogocytosis
are
often
activated
by
the
same
signal,
including
IgG
antibodies.
What
makes
a
macrophage
trogocytose
instead
of
phagocytose
not
clear.
Using
both
CD47
antibodies
Her2
Chimeric
Antigen
Receptor
(CAR)
to
induce
phagocytosis,
we
found
macrophages
preferentially
adherent
target
in
2D
cell
monolayers
3D
spheroid
models.
Disrupting
integrin
using
RGD
peptide
through
CRISPR-Cas9
knockout
αV
subunit
increased
phagocytosis.
Conversely,
increasing
adhesion
ectopically
expressing
E-Cadherin
Raji
B
targets
reduced
Finally,
examined
mitotic
cells,
naturally
occurring
example
with
adhesion.
Arresting
mitosis
significantly
Together,
our
data
show
limits
promotes
trogocytosis.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Май 26, 2025
Introduction
Macrophage
activation
is
closely
associated
with
Acute
pancreatitis
(AP).
We
screened
and
found
that
Growth
factor
receptor
bound
protein
2
(Grb2)
highly
expressed
in
macrophages
during
AP.
However,
the
relationship
between
Grb2
AP
still
poorly
understood.
In
this
study,
we
explored
role
of
Methods
for
gene
affecting
macrophage
by
combining
transcriptomics
Single-cell
RNA-sequence
analysis.
Next,
expression
M1/M2
was
detected
analysis
western
blot.
Furthermore,
effect
on
flow
cytometry.
The
severity
assessed
histological
analysis,
serum
amylase,
lipase
inflammatory
factors
vivo
.
NOD-like
thermal
domain
3
(Nlrp3)
Nuclear
kappa-B
(NF-kB)
signaling
pathways
were
also
evaluated.
Results
mainly
pancreas
up-regulated
M1
activation.
Inhibiting
could
alleviate
preventing
through
down-regulating
Nlrp3
NF-κB.
Discussion
Inhibition
can
effectively
prevent
may
potentially
be
an
effective
target
treatment
