Cells,
Journal Year:
2024,
Volume and Issue:
13(24), P. 2135 - 2135
Published: Dec. 23, 2024
Malignant
pleural
mesothelioma
is
a
neoplasm
that
often
detected
late
due
to
nonspecific
symptoms.
This
study
utilized
NSG-SGM3
mice
examine
interactions
between
human-derived
reporter
cell
line
(MZT-Luc2-mCherry)
and
the
host’s
myeloid
compartment.
Tumor
growth
was
assessed
using
optical
tomography,
while
cytokine/chemokine
production
analyzed
via
multiplex
assay.
Histological
immunohistochemical
analyses
validated
epithelioid
phenotype.
In
vitro
cells
secreted
factors
associated
with
chemoattraction
functions
supporting
previously
reported
myeloid-biased
secretory
this,
post-engraftment
analysis
revealed
increased
neutrophil-like
Ly6G+
populations
decreased
Ly6C+
inflammatory
monocytes
in
blood
of
tumor-bearing
mice.
Significant
infiltration
observed
tumor,
CD11b+
were
localized
primarily
tumor
periphery.
lysates
showed
levels
neutrophil
chemoattractants
G-CSF,
suggesting
not
role
neutrophils
progression.
novel
model
provides
platform
for
studying
mesothelioma–host
interactions,
focusing
on
It
may
also
serve
as
tool
facilitate
development
new
therapeutic
strategies
targeting
cell-mediated
mechanisms
mesothelioma.
OncoImmunology,
Journal Year:
2024,
Volume and Issue:
13(1)
Published: July 10, 2024
Attenuated
measles
virus
(MV)
exerts
its
oncolytic
activity
in
malignant
pleural
mesothelioma
(MPM)
cells
that
lack
type-I
interferon
(IFN-I)
production
or
responsiveness.
However,
other
the
tumor
microenvironment
(TME),
such
as
myeloid
cells,
possess
functional
antiviral
pathways.
In
this
study,
we
aimed
to
characterize
interplay
between
MV
and
human
MPM.
We
cocultured
MPM
cell
lines
with
monocytes
macrophages
infected
them
MV.
analyzed
transcriptome
of
each
type
studied
their
secretion
phenotypes
by
high-dimensional
flow
cytometry.
also
measured
transgene
expression
using
an
encoding
GFP
(MV-GFP).
show
drive
differentiation
into
M2-like
macrophages.
These
inhibit
harboring
a
defect
IFN-I
signaling
downstream
receptor,
while
having
minimal
effects
on
responsiveness
IFN-I.
Interestingly,
inhibition
ruxolitinib
restores
cells.
Upon
infection,
express
pro-inflammatory
genes
induce
IFN-stimulated
increases
HLA
costimulatory
molecules
phagocytic
activity.
Finally,
induces
inflammatory
cytokines,
especially
IFN-I,
PD-L1
results
reduce
viral
proteins
some
through
generate
may
stimulate
patient's
anti-tumor
immune
response.
Cancers,
Journal Year:
2023,
Volume and Issue:
15(20), P. 4962 - 4962
Published: Oct. 12, 2023
MTH1
protects
tumor
cells
and
their
supporting
endothelium
from
lethal
DNA
damage
triggered
by
oxidative
stress
in
the
microenvironment,
thus
promoting
growth.
The
impact
of
on
tumor-related
immune
compartment
remains
unknown.
We
hypothesized
that
regulates
fitness
therefore
enhances
activity
currently
used
immunotherapeutic
regimens.Our
hypotheses
were
validated
two
syngeneic
murine
mesothelioma
models
using
clinically
relevant
inhibitor,
karonudib.
also
examined
effect
combined
PD-L1
blockade
progression,
focusing
main
players.Karonudib
administration
M1
macrophage
polarization,
stimulates
CD8
expansion
promotes
activation
DC
T
cells.
Combined
inhibitors
impairs
growth
mesothelioma-associated
pleural
effusion
accumulation
more
effectively
compared
to
each
monotherapy.Combined
inhibition
holds
promise
for
successful
clinical
management
mesothelioma.
Advanced Healthcare Materials,
Journal Year:
2024,
Volume and Issue:
13(19)
Published: May 1, 2024
Immunotherapeutic
effect
is
restricted
by
the
nonimmunogenic
tumor
phenotype
and
immunosuppression
behaviors
of
tumor-associated
macrophages
(TAMs).
In
this
work,
a
drug
self-assembly
(designated
as
CeBLZ)
fabricated
based
on
chlorin
e6
(Ce6)
BLZ945
to
activate
photodynamic
immunotherapy
through
immunogenic
induction
macrophage
depletion.
It
found
that
Ce6
tends
assemble
with
without
any
excipients,
which
can
enhance
cellular
uptake,
penetration,
blood
circulation
behaviors.
The
robust
therapy
CeBLZ
efficiently
suppresses
primary
growth
also
triggers
cell
death
reverse
phenotype.
Moreover,
deplete
TAMs
in
tissues
microenvironment,
activating
abscopal
for
distant
inhibition.
vitro
vivo
results
confirm
superior
antitumor
negligible
side
effect,
might
promote
development
sophisticated
combinations
systematic
management.
Cancer Medicine,
Journal Year:
2024,
Volume and Issue:
13(21)
Published: Nov. 1, 2024
ABSTRACT
Introduction
Macrophages
are
essential
in
maintaining
homeostasis,
combating
infections,
and
influencing
the
process
of
various
diseases,
including
cancer.
originate
from
diverse
lineages:
Notably,
tissue‐resident
macrophages
(TRMs)
differ
hematopoietic
stem
cells
circulating
monocyte‐derived
based
on
genetics,
development,
function.
Therefore,
understanding
recruited
TRM
populations
is
crucial
for
investigating
disease
processes.
Methods
By
searching
literature
databses,
we
summarized
recent
relevant
studies.
Research
has
shown
that
tumor‐associated
(TAMs)
distinct
origins
accumulate
tumor
microenvironment
(TME),
with
TRM‐derived
TAMs
closely
resembling
gene
signatures
normal
TRMs.
Results
Recent
studies
have
revealed
TRMs
play
a
role
cancer
progression.
However,
organ‐specific
effects
complicate
investigations.
Nonetheless,
precise
involvement
tumors
unclear.
This
review
explores
multifaceted
roles
cancer,
presenting
insights
into
their
origins,
proliferation,
latest
research
methodologies,
impact
across
sites,
potential
strategies
as
therapeutic
targets,
interactions
other
within
TME,
internal
heterogeneity
Conclusions
We
believe
comprehensive
will
pave
way
targeted
therapies
treatment
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2024,
Volume and Issue:
43(1)
Published: Dec. 21, 2024
Abstract
Background
Malignant
pleural
mesothelioma
(MPM)
is
a
highly
chemo-refractory
and
immune-evasive
tumor
that
presents
median
overall
survival
of
12–14
months
when
treated
with
chemotherapy
immunotherapy.
New
anti-tumor
therapies
as
well
the
concomitant
reactivation
immune
destruction
are
urgently
needed
to
treat
patients
this
tumor.
The
aim
work
investigate
potential
effect
ecteinascidin
derivatives
lurbinectedin
new
first-line
treatment
option
in
MPM,
alone
combination
Methods
antitumor
activity
synthetic
analogues:
lurbinectedin,
ecubectedin
PM54
was
evaluated
an
array
patient-derived
MPM
cells
terms
cell
proliferation,
cycle,
apoptosis,
DNA
damage
repair.
Immunoblot
used
assess
cGAS/STING
pathway.
ELISA
flow
cytometry-based
assays
were
evaluate
immunogenic
death
parameters
on
immunophenotype
autologous
peripheral
blood
monocyte-MPM
co-cultures.
Patient-derived
xenografts
(PDX)
humanized
mice
efficacy
ecteinascidins
vivo.
Results
Lurbinectedin,
ecubectedin,
effective
reducing
proliferation
migration,
inducing
S-phase
cycle
arrest
malignant
cells.
These
effects
more
pronounced
compared
standard
(platinum-based
plus
pemetrexed).
Mechanistically,
drugs
downregulated
repair
genes,
activated
pathway,
promoted
release
pro-inflammatory
cytokines.
They
also
induced
cells,
enhancing
activation
CD8
+
T-cells
natural
killer
while
tumor-tolerant
T-regulatory
myeloid-derived
suppressor
ex
vivo
promising
results
observed
xenograft
models,
where
growth
increasing
ratio
anti-tumor/pro-tumor
infiltrating
populations,
either
or
combined
anti-PD-1L
atezolizumab.
Conclusions
Collectively,
these
findings
reveal
previously
unknown
mechanism
action
merits
further
investigation
for
clinical
applications
first
line
monotherapy
association
Cancers,
Journal Year:
2023,
Volume and Issue:
15(21), P. 5116 - 5116
Published: Oct. 24, 2023
Background:
Several
tumor-associated
macrophages
(TAMs)
have
shown
promise
as
prognosticators
in
cancer.
Our
aim
was
to
validate
the
importance
of
TAMs
malignant
pleural
mesothelioma
(MPM)
using
a
two-stage
design.
Methods:
We
explored
The
Cancer
Genome
Atlas
(TCGA-MESO)
select
immune-relevant
macrophage
genes
MPM,
including
M1/M2
markers,
discovery
cohort.
This
computational
cohort
used
create
multiplex
immunofluorescence
panel.
Moreover,
68
samples
MPM
paraffin
blocks
phenotypes
and
co-localization
spatial
distribution
these
immune
cells
within
TME
stromal
or
tumor
compartments.
Results:
revealed
six
(CD68,
CD86,
CD163,
CD206,
ARG1,
CD274),
complementary
were
differentially
expressed
by
M1
M2
with
distinct
roles
microenvironment
associated
prognosis.
In
addition,
immune-suppressed
MPMs
increased
enrichment
CD68,
CD163
high
densities
expressing
CD206
proteins
worse
overall
survival
(OS).
Interestingly,
below-median
distances
from
specific
M2a
M2c
OS,
suggesting
an
macrophage-driven
suppressive
component
tumors.
Conclusions:
interactions
between
situ
and,
particularly,
CD206+
are
highly
relevant
patient
outcomes.
High-resolution
technology
is
important
for
identifying
populations
tissue
specimens
potential
therapeutic
candidates
MPM.
Current Oncology Reports,
Journal Year:
2023,
Volume and Issue:
25(12), P. 1515 - 1522
Published: Nov. 28, 2023
In
this
article,
we
provide
a
comprehensive
analysis
of
recent
progress
in
the
genetic
characterisation
pleural
mesothelioma,
and
translation
these
findings
to
clinical
practice.
Advancements
sequencing
technology
have
allowed
identification
driver
mutations
improved
our
understanding
how
may
shape
mesothelioma
tumour
microenvironment.
However,
frequently
mutated
regions
including
CDKN2A,
BAP1
NF2
have,
date,
not
yet
yielded
targeted
therapy
options
that
outperform
standard
chemo-
immunotherapies.
Similarly,
association
between
mutational
profile
immune
microenvironment
or
immunotherapy
response
is
well
characterised.
Further
research
into
link
critical
for
identifying
targetable
vulnerabilities
stratifying
patients
therapy.
