Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Окт. 14, 2021
Abstract
In
the
past
decades,
transcriptomic
studies
have
revolutionized
cancer
treatment
and
diagnosis.
However,
tumor
sequencing
strategies
typically
result
in
loss
of
spatial
information,
critical
to
understand
cell
interactions
their
functional
relevance.
To
address
this,
we
investigate
gene
expression
HER2-positive
breast
tumors
using
Spatial
Transcriptomics
technology.
We
show
that
expression-based
clustering
enables
data-driven
annotation
assessment
intra-
interpatient
heterogeneity;
from
which
discover
shared
signatures
for
immune
processes.
By
integration
with
single
data,
spatially
map
tumor-associated
types
find
tertiary
lymphoid-like
structures,
a
type
I
interferon
response
overlapping
regions
T-cell
macrophage
subset
colocalization.
construct
predictive
model
infer
presence
applicable
across
tissue
technical
platforms.
Taken
together,
combine
different
data
modalities
define
high
resolution
cellular
provide
tools
generalizing
tissues
diseases.
Abstract
Background
Interferon-γ
(IFN-γ)
plays
a
key
role
in
activation
of
cellular
immunity
and
subsequently,
stimulation
antitumor
immune-response.
Based
on
its
cytostatic,
pro-apoptotic
antiproliferative
functions,
IFN-γ
is
considered
potentially
useful
for
adjuvant
immunotherapy
different
types
cancer.
Moreover,
it
may
inhibit
angiogenesis
tumor
tissue,
induce
regulatory
T-cell
apoptosis,
and/or
stimulate
the
activity
M1
proinflammatory
macrophages
to
overcome
progression.
However,
current
understanding
roles
microenvironment
(TME)
be
misleading
terms
clinical
application.
Main
body
Some
researchers
believe
has
anti-tumorigenic
properties,
while
others
suggest
that
contributes
growth
In
our
recent
work,
we
have
shown
concentration
TME
determines
function.
Further,
was
reported
tumors
treated
with
low-dose
acquired
metastatic
properties
those
infused
high
dose
led
regression.
Pro-tumorigenic
described
through
signaling
insensitivity,
downregulation
major
histocompatibility
complexes,
upregulation
indoleamine
2,3-dioxygenase,
checkpoint
inhibitors
such
as
programmed
cell
death
ligand
1.
Conclusion
Significant
research
efforts
are
required
decipher
IFN-γ-dependent
pro-
effects.
This
review
discusses
knowledge
concerning
part
complex
immune
response
cancer
highlights
importance
identifying
responsive
patients
improve
their
sensitivity
immuno-therapies.
Science,
Год журнала:
2018,
Номер
359(6377), С. 770 - 775
Опубликована: Янв. 4, 2018
SNF'ing
out
antitumor
immunity
Immune
checkpoint
inhibitors
induce
durable
tumor
regressions
in
some,
but
not
all,
cancer
patients.
Understanding
the
mechanisms
that
determine
sensitivity
to
these
drugs
could
potentially
expand
number
of
patients
who
benefit
(see
Perspective
by
Ghorani
and
Quezada).
Pan
et
al.
discovered
cells
which
a
specific
SWI/SNF
chromatin
remodeling
complex
had
been
experimentally
inactivated
were
more
sensitive
T
cell–mediated
killing.
The
responsive
interferon-γ,
leading
increased
secretion
cytokines
promote
immunity.
Miao
examined
genomic
features
tumors
from
with
metastatic
renal
cell
carcinoma
treated
immune
inhibitors.
Tumors
harboring
inactivating
mutations
PBRM1
,
encodes
subunit
same
complex,
likely
respond
drugs.
Science
this
issue
p.
770
801
;
see
also
745
Cancers,
Год журнала:
2019,
Номер
11(12), С. 2002 - 2002
Опубликована: Дек. 12, 2019
Janus
kinase-signal
transducer
and
activator
of
transcription
(JAK-STAT)
signaling
mediates
almost
all
immune
regulatory
processes,
including
those
that
are
involved
in
tumor
cell
recognition
tumor-driven
escape.
Antitumor
responses
largely
driven
by
STAT1
STAT2
induction
type
I
II
interferons
(IFNs)
the
downstream
programs
IFNs
potentiate.
Conversely,
STAT3
has
been
widely
linked
to
cancer
survival,
immunosuppression,
sustained
inflammation
microenvironment.
The
discovery
JAK-STAT
cross-regulatory
mechanisms,
post-translational
control,
non-canonical
signal
transduction
added
a
new
level
complexity
governance
over
initiation
progression.
Endeavors
better
understand
vast
effects
on
antitumor
immunity
have
unearthed
wide
range
targets,
oncogenes,
miRNAs,
other
co-regulatory
factors,
which
direct
specific
phenotypical
outcomes
subsequent
stimulation.
Yet,
rapidly
expanding
field
therapeutic
developments
aimed
resolve
aberrations
commonly
reported
multitude
cancers
marred
off-target
effects.
Here,
we
discuss
biology
context
cancer,
consequences
pathway
perturbations
current
interventions,
provide
insight
consideration
for
future
targeting
innovations.
Nature Communications,
Год журнала:
2017,
Номер
8(1)
Опубликована: Сен. 14, 2017
Abstract
Gram-negative
bacteria
actively
secrete
outer
membrane
vesicles,
spherical
nano-meter-sized
proteolipids
enriched
with
proteins,
to
the
surroundings.
Outer
vesicles
have
gained
wide
interests
as
non-living
complex
vaccines
or
delivery
vehicles.
However,
no
study
has
used
in
treating
cancer
thus
far.
Here
we
investigate
potential
of
bacterial
therapeutic
agents
treat
via
immunotherapy.
Our
results
show
remarkable
capability
effectively
induce
long-term
antitumor
immune
responses
that
can
fully
eradicate
established
tumors
without
notable
adverse
effects.
Moreover,
systematically
administered
specifically
target
and
accumulate
tumor
tissue,
subsequently
production
cytokines
CXCL10
interferon-γ.
This
effect
is
interferon-γ
dependent,
interferon-γ-deficient
mice
could
not
such
vesicle-mediated
response.
Together,
our
herein
demonstrate
effective
immunotherapeutic
agent
various
cancers
apparent
