Science Immunology,
Год журнала:
2022,
Номер
7(75)
Опубликована: Сен. 9, 2022
The
composition
of
the
gut
microbiome
can
control
innate
and
adaptive
immunity
has
emerged
as
a
key
regulator
tumor
growth,
especially
in
context
immune
checkpoint
blockade
(ICB)
therapy.
However,
underlying
mechanisms
for
how
affects
growth
remain
unclear.
Pancreatic
ductal
adenocarcinoma
(PDAC)
tends
to
be
refractory
therapy,
including
ICB.
Using
nontargeted,
liquid
chromatography–tandem
mass
spectrometry–based
metabolomic
screen,
we
identified
microbe–derived
metabolite
trimethylamine
N
-oxide
(TMAO),
which
enhanced
antitumor
PDAC.
Delivery
TMAO
intraperitoneally
or
via
dietary
choline
supplement
orthotopic
PDAC-bearing
mice
reduced
associated
with
an
immunostimulatory
tumor-associated
macrophage
(TAM)
phenotype,
activated
effector
T
cell
response
microenvironment.
Mechanistically,
potentiated
type
I
interferon
(IFN)
pathway
conferred
effects
IFN–dependent
manner.
Delivering
TMAO-primed
macrophages
intravenously
produced
similar
effects.
Combining
ICB
(anti-PD1
and/or
anti-Tim3)
mouse
model
PDAC
significantly
burden
improved
survival
beyond
alone.
Last,
levels
bacteria
containing
CutC
(an
enzyme
that
generates
trimethylamine,
precursor)
correlated
long-term
patients
anti-PD1
melanoma.
Together,
our
study
identifies
microbial
driver
lays
groundwork
potential
therapeutic
strategies
targeting
TMAO.
Cancer Discovery,
Год журнала:
2022,
Номер
12(1), С. 31 - 46
Опубликована: Янв. 1, 2022
The
hallmarks
of
cancer
conceptualization
is
a
heuristic
tool
for
distilling
the
vast
complexity
phenotypes
and
genotypes
into
provisional
set
underlying
principles.
As
knowledge
mechanisms
has
progressed,
other
facets
disease
have
emerged
as
potential
refinements.
Herein,
prospect
raised
that
phenotypic
plasticity
disrupted
differentiation
discrete
hallmark
capability,
nonmutational
epigenetic
reprogramming
polymorphic
microbiomes
both
constitute
distinctive
enabling
characteristics
facilitate
acquisition
capabilities.
Additionally,
senescent
cells,
varying
origins,
may
be
added
to
roster
functionally
important
cell
types
in
tumor
microenvironment.
SIGNIFICANCE:
Cancer
daunting
breadth
scope
its
diversity,
spanning
genetics,
tissue
biology,
pathology,
response
therapy.
Ever
more
powerful
experimental
computational
tools
technologies
are
providing
an
avalanche
"big
data"
about
myriad
manifestations
diseases
encompasses.
integrative
concept
embodied
helping
distill
this
increasingly
logical
science,
new
dimensions
presented
perspective
add
value
endeavor,
fully
understand
development
malignant
progression,
apply
medicine.
Microbial
roles
in
cancer
formation,
diagnosis,
prognosis,
and
treatment
have
been
disputed
for
centuries.
Recent
studies
provocatively
claimed
that
bacteria,
viruses,
and/or
fungi
are
pervasive
among
cancers,
key
actors
immunotherapy,
engineerable
to
treat
metastases.
Despite
these
findings,
the
number
of
microbes
known
directly
cause
carcinogenesis
remains
small.
Critically
evaluating
building
frameworks
such
evidence
light
modern
biology
is
an
important
task.
In
this
Review,
we
delineate
between
causal
complicit
trace
common
themes
their
influence
through
host's
immune
system,
herein
defined
as
immuno-oncology-microbiome
axis.
We
further
review
intratumoral
approaches
manipulate
gut
or
tumor
microbiome
while
projecting
next
phase
experimental
discovery.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Июль 1, 2021
Abstract
Emerging
data
demonstrate
that
the
activity
of
immune
cells
can
be
modulated
by
microbial
molecules.
Here,
we
show
short-chain
fatty
acids
(SCFAs)
pentanoate
and
butyrate
enhance
anti-tumor
cytotoxic
T
lymphocytes
(CTLs)
chimeric
antigen
receptor
(CAR)
through
metabolic
epigenetic
reprograming.
We
in
vitro
treatment
CTLs
CAR
with
increases
function
mTOR
as
a
central
cellular
sensor,
inhibits
class
I
histone
deacetylase
activity.
This
reprogramming
results
elevated
production
effector
molecules
such
CD25,
IFN-γ
TNF-α,
significantly
enhances
antigen-specific
ROR1-targeting
syngeneic
murine
melanoma
pancreatic
cancer
models.
Our
shed
light
onto
may
used
for
enhancing
immunity.
Collectively,
identify
two
SCFAs
therapeutic
utility
context
immunotherapy.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Июнь 14, 2022
Abstract
Reactive
oxygen
species
(ROS)
play
vital
roles
in
intestinal
inflammation.
Therefore,
eliminating
ROS
the
inflammatory
site
by
antioxidant
enzymes
such
as
catalase
and
superoxide
dismutase
may
effectively
curb
bowel
disease
(IBD).
Here,
Escherichia
coli
Nissle
1917
(ECN),
a
kind
of
oral
probiotic,
was
genetically
engineered
to
overexpress
(ECN-pE)
for
treatment
To
improve
bioavailability
ECN-pE
gastrointestinal
tract,
chitosan
sodium
alginate,
effective
biofilms,
were
used
coat
via
layer-by-layer
electrostatic
self-assembly
strategy.
In
mouse
IBD
model
induced
different
chemical
drugs,
chitosan/sodium
alginate
coating
(ECN-pE(C/A)
2
)
relieved
inflammation
repaired
epithelial
barriers
colon.
Unexpectedly,
EcN-pE(C/A)
could
also
regulate
microbial
communities
abundance
Lachnospiraceae
_NK4A136
Odoribacter
flora,
which
are
important
microbes
maintain
homeostasis.
Thus,
this
study
lays
foundation
development
living
therapeutic
proteins
using
probiotics
treat
intestinal-related
diseases.
