Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 4, 2023
Abstract
Cancer
cells
recruit
neutrophils
from
the
bloodstream
into
tumor
tissue,
where
these
immune
promote
progression
of
numerous
solid
tumors.
Studies
in
mice
suggest
that
blocking
neutrophil
recruitment
to
tumors
by
inhibition
chemokine
receptor
CXCR2
could
be
a
potential
immunotherapy
for
pancreatic
cancer.
Yet,
mechanisms
which
humans,
as
well
how
potentially
serve
cancer
therapy,
remain
elusive.
In
this
study,
we
developed
human
cell-based
microphysiological
system
quantify
neutrophil-tumor
spheroid
interactions
both
“separated”
and
“contact”
scenarios.
We
found
invasion
spheroids
through
secretion
soluble
factors
direct
contact
with
cells.
However,
they
proliferation
solely
contact.
Interestingly,
treatment
AZD-5069,
inhibitor,
attenuates
neutrophils.
Our
findings
show
reduces
migration
toward
spheroids.
These
results
shed
new
light
on
tumor-promoting
tumor-suppressive
may
aid
design
optimization
novel
immunotherapeutic
strategies
based
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2024,
Volume and Issue:
43(1)
Published: March 19, 2024
Abstract
Background
In
clear
cell
renal
carcinoma
(ccRCC),
first-line
treatment
combines
nivolumab
(anti-PD-1)
and
ipilimumab
(anti-CTLA4),
yielding
long-term
remissions
but
with
only
a
40%
success
rate.
Our
study
explored
the
potential
of
enhancing
ccRCC
by
concurrently
using
CXCR2
inhibitors
alongside
immunotherapies.
Methods
We
analyzed
ELR
+
CXCL
levels
their
correlation
patient
survival
during
immunotherapy.
RCT001,
unique
inhibitor,
was
examined
for
its
mechanism
action,
particularly
effects
on
human
primary
macrophages.
tested
synergistic
impact
RCT001
in
combination
immunotherapies
both
mouse
models
presence
PBMC.
Resuts
Elevated
cytokine
were
found
to
correlate
reduced
overall
our
optimized
compound,
acted
as
an
inverse
agonist,
effectively
inhibiting
angiogenesis
reducing
viability
cells.
It
redirected
M2-like
macrophages
without
affecting
M1-like
macrophage
polarization
directed
against
tumor.
models,
enhanced
efficacy
anti-CTLA4
anti-PD1
tumor-associated
M2
neutrophils.
also
impacted
activation
CD4
T
lymphocytes,
immune-tolerant
lymphocytes
while
increasing
activated
natural
killer
dendritic
Similar
effectiveness
observed
RCC
tumors
when
combined
anti-PD-1
treatment.
Conclusions
through
mechanism,
suppresses
proliferation,
angiogenesis,
polarization.
This
optimization
potentiates
immunotherapy
holds
promise
significantly
improving
prospects
metastatic
patients.
Cancer Letters,
Journal Year:
2024,
Volume and Issue:
588, P. 216778 - 216778
Published: March 6, 2024
This
study
aims
to
investigate
applicable
robust
biomarkers
that
can
improve
prognostic
predictions
for
colorectal
liver
metastasis
(CRLM)
patients
receiving
simultaneous
resection.
A
total
of
1323
CRLM
from
multiple
centres
were
included.
The
preoperative
aspartate
aminotransferase
platelet
ratio
index
(APRI)
level
blood
obtained.
Patients
stratified
into
a
high
APRI
group
and
low
group,
comparisons
conducted
by
analyzing
progression-free
survival
(PFS),
overall
(OS)
postoperative
early
recurrence.
Tumour
samples
collected
perform
single-cell
RNA
sequencing
multiplex
immunohistochemistry/immunofluorescence
(mIHC/IF)
the
association
levels
tumour
microenvironment
CRLM.
Compared
with
<0.33,
PFS
disadvantage
(IPTW-adjusted
HR
=
1.240,
P
0.015)
OS
(IPTW-
adjusted
1.507,
0.002)
≥0.33
preserved
in
IPTW-adjusted
Cox
hazards
regression
analyses.
An
≥0.25
was
associated
significantly
increased
risk
recurrence
after
adjustment
OR
1.486,
0.001).
external
validation
showed
consistent
results
training
cohort.
In
revealed
heightened
malignancy
epithelial
cells,
enrichment
inflammatory-like
cancer-associated
fibroblasts
SPP1+
macrophages
activation
malignant
cells
fibrotic
microenvironment,
more
suppressed-function
T
cells;
mIHC/IF
PD1+
CD4+
FOXP3+
CD8+
iCAFs
intratumoral
region
peritumoral
region.
contributed
valuable
evidence
regarding
predicting
prognoses
among
resection
provided
underlying
clues
supporting
between
clinical
outcomes
bioinformatics
analysis
mIHC/IF.
Biomedicines,
Journal Year:
2023,
Volume and Issue:
11(10), P. 2621 - 2621
Published: Sept. 24, 2023
Conventional
and
cancer
immunotherapies
encompass
diverse
strategies
to
address
various
types
stages.
However,
combining
these
approaches
often
encounters
limitations
such
as
non-specific
targeting,
resistance
development,
high
toxicity,
leading
suboptimal
outcomes
in
many
cancers.
The
tumor
microenvironment
(TME)
is
orchestrated
by
intricate
interactions
between
immune
non-immune
cells
dictating
progression.
An
innovative
avenue
therapy
involves
leveraging
small
molecules
influence
a
spectrum
of
resistant
cell
populations
within
the
TME.
Recent
discoveries
have
unveiled
phenotypically
cohort
innate-like
T
(ILT)
hybrid
(HCs)
exhibiting
novel
characteristics,
including
augmented
proliferation,
migration,
exhaustion,
evasion
immunosurveillance,
reduced
apoptosis,
drug
resistance,
heightened
metastasis
frequency.
Leveraging
small-molecule
immunomodulators
target
players
presents
an
exciting
frontier
developing
immunotherapies.
Moreover,
molecule
modulators
with
immunotherapy
can
synergistically
enhance
inhibitory
impact
on
progression
empowering
system
meticulously
fine-tune
responses
TME,
bolstering
its
capacity
recognize
eliminate
cells.
This
review
outlines
involving
that
modify
potentially
revolutionizing
therapeutic
interventions
enhancing
anti-tumor
response.
Cancers,
Journal Year:
2024,
Volume and Issue:
16(16), P. 2797 - 2797
Published: Aug. 8, 2024
This
review
delves
into
the
intricate
roles
of
interleukin-8
(IL-8)
and
its
receptors,
CXCR1
CXCR2,
in
prostate
cancer
(PCa),
particularly
castration-resistant
(CRPC)
metastatic
CRPC
(mCRPC).
emphasizes
crucial
role
tumour
microenvironment
(TME)
inflammatory
cytokines
promoting
progression
response
to
cell
targeting
agents.
IL-8,
acting
through
C-X-C
chemokine
receptor
type
1
(CXCR1)
2
(CXCR2),
modulates
multiple
signalling
pathways,
enhancing
angiogenesis,
proliferation,
migration
cells.
highlights
shift
PCa
research
focus
from
solely
cells
non-cancer-cell
components,
including
vascular
endothelial
cells,
extracellular
matrix,
immune
dynamic
interactions
within
TME.
The
immunosuppressive
nature
TME
significantly
influences
resistance
emerging
therapies.
Current
treatment
modalities,
androgen
deprivation
therapy
chemotherapeutics,
encounter
persistent
are
complicated
by
cancer’s
notably
“immune-cold”
nature,
which
limits
system
tumour.
These
challenges
underscore
critical
need
for
novel
approaches
that
both
overcome
enhance
engagement
therapeutic
potential
inhibiting
IL-8
is
explored,
with
studies
showing
enhanced
sensitivity
treatments,
radiation
inhibitors.
Clinical
trials,
such
as
ACE
trial,
demonstrate
efficacy
combining
CXCR2
inhibitors
existing
offering
significant
benefits,
especially
patients
resistant
PCa.
also
addresses
chemokines,
noting
complexity
precision
avoid
side
effects
optimize
outcomes.
Advanced Functional Materials,
Journal Year:
2023,
Volume and Issue:
34(10)
Published: Nov. 23, 2023
Abstract
The
progress
of
precision
oncology
medicine
is
always
limited
by
the
tumor
off‐targeting,
drug
side
effects,
and
treatment
inefficiency
due
to
complex
ever‐changing
microenvironment.
Living
cells,
such
as
blood
cells
immune
exhibit
natural
tropism,
controllable
physicochemical
modification,
excellent
biocompatibility,
which
provide
an
advantageous
pathway
for
innovative
efficient
suppression.
Armed
with
nanoengineering
techniques,
artificial
living
harness
their
inherent
biological
properties
precisely
identify
eradicate
tumors,
demonstrating
broad
application
prospects
great
transformational
potential
in
personalized
cancer
therapy.
Here,
recent
advances
cell‐based
bionanobots
including
platelets,
red
neutrophil,
macrophage,
CAR‐T
therapy
regulation
are
summarized,
anti‐tumor
strategies
engineering
cell
nanorobots
overcome
barriers
suppression
also
outlined
(e.g.,
immunotherapy,
sonodynamic
therapy,
chemo/radiotherapy,
phototherapy).
In
addition,
study
discusses
advantages,
limitations,
current
challenges
delivery
systems,
perspectives
on
future
development
cell‐mediated
nanomedicine.
Biomolecules,
Journal Year:
2025,
Volume and Issue:
15(5), P. 645 - 645
Published: April 30, 2025
Pancreatic
ductal
adenocarcinoma
(PDAC)
has
one
of
the
lowest
5-year
survival
rates
all
cancers,
and
limited
treatment
options
exist.
Immunotherapy
is
effective
in
some
cancer
types,
but
immunosuppressive
tumor
microenvironment
(TME)
PDAC
a
barrier
to
immunotherapy.
CXCR2+
myeloid-derived
suppressor
cells
(MDSCs)
are
abundant
tumors
humans
mouse
models.
MDSCs
suppress
effector
cell
function,
making
them
attractive
targets
for
restoring
anti-tumor
immunity.
In
this
study,
we
show
that
most
soluble
factors
released
from
genetically
diverse
set
human
CXCR2
ligands,
including
CXCL8,
CXCL5,
CXCL1.
Expression
ligands
at
least
partially
dependent
on
mutant
KRAS
NFκB
signaling,
which
two
commonly
dysregulated
pathways
PDAC.
We
prevalent
immune
tumors.
expressed
high
levels
CXCR2,
found
myeloid
readily
migrate
toward
conditioned
media
(CM)
prepared
cultures.
designed
ligand-Fc
fusion
proteins
modulate
chemotactic
signaling
axis.
Unexpectedly,
these
were
superior
native
chemokines
binding
activation
cells.
These
“superkines”
potent
inhibitors
CM-induced
migration
small-molecule
neutralizing
antibodies.
Our
findings
suggest
superkines
may
disrupt
recruitment
tumors,
ultimately
improving
immunotherapy
outcomes
patients
with
