Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Фев. 13, 2023
The
tumor
microenvironment
(TME)
in
pancreatic
ductal
adenocarcinoma
(PDAC)
is
a
complex
ecosystem
that
drives
progression;
however,
in-depth
single
cell
characterization
of
the
PDAC
TME
and
its
role
response
to
therapy
lacking.
Here,
we
perform
single-cell
RNA
sequencing
on
freshly
collected
human
samples
either
before
or
after
chemotherapy.
Overall,
find
heterogeneous
mixture
basal
classical
cancer
subtypes,
along
with
distinct
cancer-associated
fibroblast
macrophage
subpopulations.
Strikingly,
basal-like
cells
exhibit
similar
transcriptional
responses
chemotherapy
do
not
demonstrate
shift
towards
program
among
treated
samples.
We
observe
decreased
ligand-receptor
interactions
samples,
particularly
between
TIGIT
CD8
+
T
receptor
cells,
identify
as
major
inhibitory
checkpoint
molecule
cells.
Our
results
suggest
profoundly
impacts
may
promote
resistance
immunotherapy.
Clinical Cancer Research,
Год журнала:
2022,
Номер
29(1), С. 244 - 260
Опубликована: Окт. 14, 2022
Abstract
Purpose:
The
liver
is
the
most
frequent
metastatic
site
for
colorectal
cancer.
Its
microenvironment
modified
to
provide
a
niche
that
conducive
cancer
cell
growth.
This
study
focused
on
characterizing
cellular
changes
in
(mCRC)
tumor
(TME).
Experimental
Design:
We
analyzed
series
of
microsatellite
stable
(MSS)
mCRCs
liver,
paired
normal
tissue,
and
peripheral
blood
mononuclear
cells
using
single-cell
RNA
sequencing
(scRNA-seq).
validated
our
findings
multiplexed
spatial
imaging
bulk
gene
expression
with
deconvolution.
Results:
identified
TME-specific
SPP1-expressing
macrophages
altered
metabolism
features,
foam
characteristics,
increased
activity
extracellular
matrix
(ECM)
organization.
SPP1+
fibroblasts
expressed
complementary
ligand–receptor
pairs
potential
mutually
influence
their
gene-expression
programs.
TME
lacked
dysfunctional
CD8
T
contained
regulatory
cells,
indicative
immunosuppression.
Spatial
these
states
TME.
Moreover,
had
close
proximity,
which
requirement
intercellular
communication
networking.
In
an
independent
cohort
we
confirmed
presence
data.
An
proportion
was
associated
worst
prognosis
patients.
Conclusions:
demonstrated
mCRC
characterized
by
transcriptional
alterations
Intercellular
networking
between
supports
growth
immunosuppressed
liver.
These
features
can
be
used
target
immune-checkpoint–resistant
MSS
tumors.
Journal of Hepatology,
Год журнала:
2023,
Номер
80(4), С. 634 - 644
Опубликована: Дек. 30, 2023
The
liver
is
one
of
the
organs
most
commonly
affected
by
metastasis.
presence
metastases
has
been
reported
to
be
responsible
for
an
immunosuppressive
microenvironment
and
diminished
immunotherapy
efficacy.
Herein,
we
aimed
investigate
role
IL-10
in
metastasis
determine
how
its
modulation
could
affect
efficacy
vivo.
Abstract
Alpha-fetoprotein
(AFP)-secreting
hepatocellular
carcinoma
(HCC),
which
accounts
for
~75%
of
HCCs,
is
more
aggressive
with
a
worse
prognosis
than
those
without
AFP
production.
The
mechanism
through
the
interaction
between
tumors
and
microenvironment
leads
to
distinct
phenotypes
not
yet
clear.
Therefore,
our
study
aims
identify
characteristic
features
potential
treatment
targets
AFP-negative
HCC
(ANHC)
AFP-positive
(APHC).
We
utilized
single-cell
RNA
sequencing
analyze
6
ANHC,
APHC,
4
adjacent
normal
tissues.
Integrated
multi-omics
analysis
together
survival
were
also
performed.
Further
validation
was
conducted
via
cytometry
time-of-flight
on
30
HCCs
multiplex
immunohistochemistry
additional
59
HCCs.
Our
data
showed
that
genes
related
antigen
processing
interferon-γ
response
abundant
in
tumor
cells
APHC.
Meanwhile,
APHC
associated
multifaceted
immune
distortion,
including
exhaustion
diverse
T
cell
subpopulations,
accumulation
tumor-associated
macrophages
(TAMs).
Notably,
TAM-SPP1
+
highly
enriched
as
its
receptor
CD44
cells.
Targeting
Spp1-Cd44
axis
restored
function
vitro
significantly
reduced
burden
when
treated
either
anti-Spp1
or
anti-Cd44
antibody
alone
combination
anti-Pd-1
mouse
model.
Furthermore,
elevated
IL6
TGF-β1
signaling
contributed
enrichment
In
conclusion,
this
uncovered
suppressive
highlighted
role
regulating
microenvironment,
thereby
revealing
SPP1-CD44
promising
target
achieving
favorable
treatment.
Clinical and Translational Medicine,
Год журнала:
2023,
Номер
13(2)
Опубликована: Фев. 1, 2023
Abstract
Background
Dendritic
cells
(DCs)
mediate
divergent
immune
effects
by
activating
T
or
negatively
regulating
the
response
to
promote
tolerance.
They
perform
specific
functions
determined
their
tissue
distribution
and
maturation
state.
Traditionally,
immature
semimature
DCs
were
described
have
immunosuppressive
effects,
leading
Nonetheless,
recent
research
has
demonstrated
that
mature
can
also
suppress
under
certain
circumstances.
Main
body
Mature
enriched
in
immunoregulatory
molecules
(mregDCs)
emerged
as
a
regulatory
module
across
species
tumour
types.
Indeed,
distinct
roles
of
mregDCs
immunotherapy
sparked
interest
researchers
field
single‐cell
omics.
In
particular,
these
found
be
associated
with
positive
favourable
prognosis.
Conclusion
Here,
we
provide
general
overview
latest
most
notable
advances
findings
regarding
basic
features
complex
nonmalignant
diseases
microenvironment.
We
emphasise
important
clinical
implications
tumours.
