Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Окт. 6, 2022
As
the
essential
regulators
of
organ
fibrosis,
macrophages
undergo
marked
phenotypic
and
functional
changes
after
injury.
These
in
macrophage
phenotype
function
can
result
maladaptive
repair,
causing
chronic
inflammation
development
pathological
fibrosis.
Autophagy,
a
highly
conserved
lysosomal
degradation
pathway,
is
one
major
players
to
maintain
homeostasis
through
clearing
protein
aggregates,
damaged
organelles,
invading
pathogens.
Emerging
evidence
has
shown
that
autophagy
plays
an
role
polarization,
inflammation,
Because
high
heterogeneity
different
organs,
types
may
play
roles
Here,
we
review
current
understanding
fibrosis
highlight
potential
treatment
Finally,
important
unresolved
issues
this
field
are
briefly
discussed.
A
better
mechanisms
contribute
developing
novel
therapies
for
inflammatory
diseases
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Янв. 6, 2023
Abstract
Immune
checkpoint
therapy
in
breast
cancer
remains
restricted
to
triple
negative
patients,
and
long-term
clinical
benefit
is
rare.
The
primary
aim
of
immune
blockade
prevent
or
reverse
exhausted
T
cell
states,
but
exhaustion
tumors
not
well
understood.
Here,
we
use
single-cell
transcriptomics
combined
with
imaging
mass
cytometry
systematically
study
environments
human
that
either
do
contain
cells,
a
focus
on
luminal
subtypes.
We
find
the
presence
PD-1
high
exhaustion-like
phenotype
associated
an
inflammatory
environment
characteristic
cytotoxic
profile,
increased
myeloid
activation,
evidence
for
elevated
immunomodulatory,
chemotactic,
cytokine
signaling,
accumulation
natural
killer
cells.
Tumors
harboring
exhausted-like
cells
show
expression
MHC-I
tumor
CXCL13
as
altered
spatial
organization
more
immature
rather
than
mature
tertiary
lymphoid
structures.
Our
data
reveal
fundamental
differences
between
without
within
cancer,
–
PD-L1
are
strong
distinguishing
features
these
environments.
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.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Окт. 10, 2022
Brain
metastases
(BrMs)
are
a
common
occurrence
in
lung
cancer
with
dismal
outcome.
To
understand
the
mechanism
of
metastasis
to
inform
prognosis
and
treatment,
here
we
analyze
primary
metastasized
tumor
specimens
from
44
non-small
cell
patients
by
spatial
RNA
sequencing,
affording
whole
transcriptome
map
resolved
morphological
markers
for
core,
immune
microenvironment
(TIME),
brain
(TBME).
Our
data
indicate
that
(TME)
brain,
including
TIME
TBME,
undergoes
extensive
remodeling
create
an
immunosuppressive
fibrogenic
niche
BrMs.
Specifically,
TME
is
characterized
reduced
antigen
presentation
B/T
function,
increased
neutrophils
M2-type
macrophages,
immature
microglia,
reactive
astrocytes.
Differential
gene
expression
network
analysis
identify
fibrosis
regulation
as
major
functional
modules
disrupted
both
TME.
Besides
providing
systems-level
insights
into
metastasis,
our
study
uncovers
potential
prognostic
biomarkers
suggests
therapeutic
strategies
should
be
tailored
status
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Окт. 6, 2022
As
the
essential
regulators
of
organ
fibrosis,
macrophages
undergo
marked
phenotypic
and
functional
changes
after
injury.
These
in
macrophage
phenotype
function
can
result
maladaptive
repair,
causing
chronic
inflammation
development
pathological
fibrosis.
Autophagy,
a
highly
conserved
lysosomal
degradation
pathway,
is
one
major
players
to
maintain
homeostasis
through
clearing
protein
aggregates,
damaged
organelles,
invading
pathogens.
Emerging
evidence
has
shown
that
autophagy
plays
an
role
polarization,
inflammation,
Because
high
heterogeneity
different
organs,
types
may
play
roles
Here,
we
review
current
understanding
fibrosis
highlight
potential
treatment
Finally,
important
unresolved
issues
this
field
are
briefly
discussed.
A
better
mechanisms
contribute
developing
novel
therapies
for
inflammatory
diseases
