bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 4, 2024
ABSTRACT
While
immune
checkpoint
inhibitors
have
demonstrated
durable
responses
in
various
cancer
types,
a
significant
proportion
of
patients
do
not
exhibit
favourable
to
these
interventions.
To
uncover
potential
factors
associated
with
positive
response
immunotherapy,
we
established
bilateral
tumor
model
using
P815
mastocytoma
implanted
DBA/2
mice.
In
this
model,
only
fraction
tumor-bearing
mice
responds
favourably
anti-PD-1
treatment,
thus
providing
valuable
explore
the
influence
microenvironment
(TME)
determining
efficacy
blockade
(ICB)-based
immunotherapies.
Moreover,
allows
for
analysis
pretreatment
and
inference
its
treatment
outcome
based
on
observed
contralateral
tumor.
Here,
that
tumor-reactive
CD8
+
T
cell
clones
expressing
high
levels
Tim-3
were
anti-tumor
following
administration.
Our
study
also
revealed
distinct
differentiation
dynamics
tumor-infiltrating
myeloid
cells
responding
non-responding
An
IFNγ-enriched
TME
appeared
promote
monocytes
into
PD-L1
pos
MHC
II
immunotherapy.
Monocytes
present
failed
reach
same
final
stage
trajectory,
suggesting
an
altered
monocyte
macrophage
route
may
hamper
ICB.
These
insights
will
direct
future
research
towards
temporal
TAMs,
aiming
identify
responsible
transitions
between
states
within
TME.
This
approach
potentially
pave
way
novel
strategies
enhance
PD-1
blockade.
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 16, 2024
Abstract
Background
and
objectives
Immunotherapies
targeting
PD-1
CTLA-4
are
key
components
of
the
treatment
metastatic
clear
cell
renal
carcinoma
(mccRCC).
However,
they
have
distinct
safety
profiles
resistance
to
can
occur.
We
assess
soluble
TIM-3
(sTIM-3)
in
plasma
mccRCC
patients
as
a
potential
theranostic
biomarker,
well
its
source
biological
significance.
Methods
analyzed
association
sTIM-3
with
overall
survival
(OS),
tumor
response,
common
clinical
factors
across
two
cohorts
treated
anti-PD-1
(n
=
27),
anti-
or
+
anti-CTLA-4
124).
The
origin
role
studied
on
blood
samples,
using
multiplex
immunohistochemistry
flow
cytometry
syngeneic
model
antitumor
vaccination.
also
reanalyzed
publicly
available
single-cell
transcriptomic
(scRNAseq)
data
mass
data.
Key
findings
limitations
is
elevated
shows
associations
vs
anti-CTLA-4.
independent
from
other
factors.
Myeloid
immune
cells
appear
prominent
sTIM-3,
which
may
indicate
their
dysfunctional
response.
Future
investigations
warranted
antiangiogenic
therapies.
Further
functional
studies
needed
confirm
value
clarify
Conclusions
implications
appears
be
promising
biomarker
for
optimizing
strategies
ccRCC
therapeutic
target.
DNA
logic
gates
with
dynamic
nanostructures
have
made
a
profound
impact
on
cancer
diagnosis
and
treatment.
Through
programming
the
structure
changes
of
nanodevices,
precise
molecular
recognition
signal
amplification
smart
therapeutic
strategies
been
reported.
This
enhances
specificity
sensitivity
theranostics,
improves
precision
treatment
outcomes.
review
explores
basic
components
corresponding
gates,
as
well
their
applications
for
therapies.
The
would
contribute
to
early
detection
personalized
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 4, 2024
ABSTRACT
While
immune
checkpoint
inhibitors
have
demonstrated
durable
responses
in
various
cancer
types,
a
significant
proportion
of
patients
do
not
exhibit
favourable
to
these
interventions.
To
uncover
potential
factors
associated
with
positive
response
immunotherapy,
we
established
bilateral
tumor
model
using
P815
mastocytoma
implanted
DBA/2
mice.
In
this
model,
only
fraction
tumor-bearing
mice
responds
favourably
anti-PD-1
treatment,
thus
providing
valuable
explore
the
influence
microenvironment
(TME)
determining
efficacy
blockade
(ICB)-based
immunotherapies.
Moreover,
allows
for
analysis
pretreatment
and
inference
its
treatment
outcome
based
on
observed
contralateral
tumor.
Here,
that
tumor-reactive
CD8
+
T
cell
clones
expressing
high
levels
Tim-3
were
anti-tumor
following
administration.
Our
study
also
revealed
distinct
differentiation
dynamics
tumor-infiltrating
myeloid
cells
responding
non-responding
An
IFNγ-enriched
TME
appeared
promote
monocytes
into
PD-L1
pos
MHC
II
immunotherapy.
Monocytes
present
failed
reach
same
final
stage
trajectory,
suggesting
an
altered
monocyte
macrophage
route
may
hamper
ICB.
These
insights
will
direct
future
research
towards
temporal
TAMs,
aiming
identify
responsible
transitions
between
states
within
TME.
This
approach
potentially
pave
way
novel
strategies
enhance
PD-1
blockade.
