Cell Reports Medicine,
Год журнала:
2024,
Номер
unknown, С. 101882 - 101882
Опубликована: Дек. 1, 2024
Platinum-based
chemotherapy
in
combination
with
anti-PD-L1
antibodies
has
shown
promising
results
mesothelioma.
However,
the
immunological
mechanisms
underlying
its
efficacy
are
not
well
understood
and
there
no
predictive
biomarkers
to
guide
treatment
decisions.
Here,
we
combine
time
course
RNA
sequencing
(RNA-seq)
of
peripheral
blood
mononuclear
cells
pre-treatment
tumor
transcriptome
data
from
single-arm,
phase
2
DREAM
trial
(N
=
54).
Single-cell
RNA-seq
T
cell
receptor
(TCR-seq)
reveal
that
CD8
Abstract
Cancer
disrupts
intratumoral
innate-adaptive
immune
crosstalk,
but
how
the
systemic
landscape
evolves
during
breast
cancer
progression
remains
unclear.
We
profiled
circulating
cells
in
stage
I–III
and
IV
triple-negative
(TNBC)
patients
healthy
donors
(HDs).
Metastatic
TNBC
(mTNBC)
had
reduced
T
cells,
dendritic
differentiated
B
compared
to
non-metastatic
HDs,
partly
linked
prior
chemotherapy.
Vδ1
γδ
from
mTNBC
produced
more
IL17
than
those
HDs.
Chemotherapy-naïve
showed
increased
classical
monocytes
neutrophils.
Transcriptional,
proteomic,
functional
analyses
revealed
that
neutrophils
exhibited
enhanced
migratory
capacity,
elevated
granule
proteins,
higher
ROS
production.
Some
changes,
such
as
non-switched
heightened
neutrophil
migration,
were
evident
earlier
stages.
This
study
comprehensively
maps
immunity
TNBC,
guiding
future
research
on
patient
stratification
immunomodulation
strategies.
Immune
checkpoint
blockade
(ICB)
therapy,
including
antibodies
targeting
the
programmed
cell
death
protein
1
(PD-1)
pathway,
has
significantly
prolonged
overall
survival
(OS)
in
patients
with
advanced
cervical
cancer
(CC).
ICB
treatment
affects
both
target
cells
and
various
components
released
by
immune
cells,
which
can
be
observed
peripheral
blood.
However,
there
been
limited
research
on
dynamics
of
blood
immunophenotyping
its
association
OS
CC
receiving
therapy.
Patients
persistent,
recurrent,
or
metastatic
treated
were
enrolled
between
December
2019
September
2022.
The
dynamic
changes
immunoglobulins,
complement
analyzed
at
baseline
(within
30
days
prior
to
first
cycle)
after
second
cycle
(4-6
weeks
treatment).
Associations
levels
using
multivariable
Cox
regression
analysis.
In
this
retrospective
cohort
study,
119
who
received
least
two
cycles
included.
Data
available
for
70
these
patients.
percentages
suppressor
T
(Ts)
natural
killer
(NK)
increased
post-ICB
treatment,
whereas
Th/Ts
ratio
IgM
decreased.
cytotoxic
(Tc)
Ts
ratio,
IgM,
IgA,
C3,
C4
associated
Furthermore,
analysis
found
that
a
high
level
IgA
was
poor
(HR
=
2.918;
95%
CI,
1.081-7.877,
P
0.035).
Our
study
demonstrated
potential
proliferation
anti-tumor
some
undergoing
associations
suggest
biomarkers
might
have
as
prognostic
tools.
Clinical and Translational Medicine,
Год журнала:
2025,
Номер
15(3)
Опубликована: Фев. 25, 2025
Immunotherapy
shows
promise
for
treating
advanced
breast
cancer,
but
only
a
few
patients
could
respond.
Predictive
biomarkers
from
peripheral
blood
are
urgently
needed.
We
designed
comprehensive
42-marker
mass
cytometry
panel
to
profile
the
samples
57
diagnosed
with
HER2-negative
cancer
receiving
anti-PD-1
combination
therapy.
Patients
were
categorized
as
responders
and
non-responders
according
6-month
progression-free
survival
(PFS),
followed
by
phenotypic
functional
comparations
identify
candidate
predictive
biomarkers.
Longitudinal
analysis
of
paired
further
revealed
dynamic
changes
in
these
specific
subpopulations.
Non-responders
exhibited
significantly
higher
frequencies
CD39+
Tregs
(adjusted
p
=
.031)
T-cell
milieu
at
baseline,
which
positive
correlation
PD-1+
T
cells
NR
group.
assessment
indicated
significant
decrease
an
increase
following
treatment,
suggesting
their
potential
role
immunotherapy
resistance.
In
myeloid
compartment,
showed
CCR2+
monocyte-derived
dendritic
cell
than
.037).
These
positively
correlated
other
negatively
naïve
non-responders.
Based
on
two
efficacy-related
biomarkers,
we
developed
prognostic
prediction
model
confirmed
its
superiority
distinguishing
patient
PFS
(p
<
.001).
Peripheral
response,
serving
guide
therapeutic
choices
immunotherapy.
associated
poor
response
cancer.
Higher
correlate
better
outcomes.
A
based
effectively
distinguishes
survival.
offer
non-invasive
approach
choices.
Immunotherapy
targeting
programmed
cell
death-1
(PD-1)
and
PD-L1
immune
checkpoints
has
reshaped
treatment
paradigms
across
several
cancers,
including
breast
cancer.
Combining
PD-1/PD-L1
checkpoint
blockade
(ICB)
with
chemotherapy
shown
promising
efficacy
in
both
early
metastatic
triple-negative
cancer,
although
only
a
subset
of
patients
experiences
durable
responses.
Identifying
responders
optimizing
drug
selection
are
therefore
critical.
The
effectiveness
immunotherapy
depends
on
tumor-intrinsic
factors
the
extrinsic
cell-cell
interactions
within
tumor
microenvironment
(TME).
This
review
systematically
summarizes
key
findings
from
clinical
trials
ICBs
cancer
examines
mechanisms
underlying
expression
regulation.
We
also
highlight
recent
advances
identifying
potential
biomarkers
for
therapy
emerging
evidence
TME
alterations
following
treatment.
Among
these,
quantity,
immunophenotype,
spatial
distribution
tumor-infiltrating
lymphocytes
stand
out
as
biomarkers.
Additionally,
we
explore
strategies
to
enhance
aiming
support
development
personalized
approaches
tailored
unique
characteristics
each
patient's
tumor.
Life,
Год журнала:
2024,
Номер
14(7), С. 833 - 833
Опубликована: Июнь 29, 2024
Cancer
remains
a
significant
global
health
challenge
due
to
its
high
morbidity
and
mortality
rates.
Early
detection
is
essential
for
improving
patient
outcomes,
yet
current
diagnostic
methods
lack
the
sensitivity
specificity
needed
identifying
early-stage
cancers.
Here,
we
explore
potential
of
multi-omics
approaches,
which
integrate
genomic,
transcriptomic,
proteomic,
metabolomic
data,
enhance
early
cancer
detection.
We
highlight
challenges
benefits
data
integration
from
these
diverse
sources
discuss
successful
examples
applications
in
other
fields.
By
leveraging
advanced
technologies,
can
significantly
improve
diagnostics,
leading
better
outcomes
more
personalized
care.
underscore
transformative
approaches
revolutionizing
need
continued
research
clinical
integration.
Deleted Journal,
Год журнала:
2025,
Номер
33(1), С. 200933 - 200933
Опубликована: Янв. 14, 2025
Metabolic
features
are
crucial
in
tumor
immune
interactions,
but
their
relationship
with
antitumor
responses
is
not
yet
fully
understood.
This
study
used
Mendelian
randomization
analysis
to
identify
the
causal
relationships
between
blood
metabolites
and
cells
evaluate
effects
of
metabolic
pathways
reactions
on
various
cancers.
Levels
156
exhibited
significant
associations
selected
cells.
enrichment
indicated
laurate,
propionyl-carnitine,
carnitine
l-acetylcarnitine
enriched
fatty
acid
(FA)
metabolism
pathways.
These
significantly
correlated
CD8+
T
cell
function
signatures
environment
favor
better
prognostic
outcomes.
contributing
immunotherapy
were
identified
establish
immuno-metabolic
reaction
score
(IMRS).
IMRS
infiltration
levels
signature
scores
either
10×
Visium
spatial
transcriptomic
or
RNA-seq
samples.
Finally,
could
predict
favorable
survival
outcomes
different
cancer
patients
treated
immunotherapy.
Our
revealed
a
link
certain
related
landscape
functions.
results
promote
accurate
stratification
before
treatment
improve
efficacy
Multiple
studies
have
demonstrated
that
the
abundance
and
functionality
of
γδ
T
cells
are
favorable
prognostic
indicators
for
prolonged
survival
in
cancer
patients.
However,
association
between
immunophenotype
circulating
therapeutic
response
NSCLC
patients
undergoing
chemotherapy
or
targeted
therapy
remains
unclear.
Patients
with
EGFR
wild-type
(EGFR-WT)
mutant
(EGFR-Mut)
non-small
cell
lung
(NSCLC),
diagnosed
January
2020
2024,
were
included
this
study.
Clinicopathological
characteristics,
treatment
regimens,
follow-up
data
retrospectively
collected.
Peripheral
blood
samples
from
52
analyzed
immunophenotypes
αβ
using
full-spectrum
flow
cytometry.
No
significant
differences
observed
proportions
cells,
nor
expression
immune
exhaustion
markers,
epidermal
growth
factor
receptor
Notably,
a
high
clinical
benefit
rate
(responder,
R)
exhibited
higher
proportion
Vδ2
compared
to
non-responders
(NR),
both
EGFR-Mut
(NR
vs.
R,
P
=
0.0437)
EGFR-WT
groups
0.0180).
Additionally,
marker
PD-1
on
was
significantly
lower
responder
group
EGFR-Mut,
0.0050;
EGFR-WT,
Moreover,
elevated
levels
TNF-α
non-responders,
irrespective
mutation
status
0.0055;
0.0007).
These
findings
collectively
suggest
low
critical
contributors
effectiveness
therapies
NSCLC.
Targeting
may
represent
promising
strategy
enhancing
rates
Studies
investigating
the
clinical
benefits
of
obesity
across
various
cancer
types
are
limited.
This
big
data
study
demonstrates
that
is
associated
with
improved
overall
survival
up
to
5
years
after
treatment
immune
checkpoint
inhibition
solid
tumor
malignancies.
