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.
Gut,
Год журнала:
2022,
Номер
71(7), С. 1412 - 1425
Опубликована: Март 11, 2022
Despite
the
promising
advances
in
novel
cancer
therapy
such
as
immune
checkpoint
inhibitors
(ICIs),
limitations
including
therapeutic
resistance
and
toxicity
remain.
In
recent
years,
relationship
between
gut
microbiota
has
been
extensively
studied.
Accumulating
evidence
reveals
role
of
defining
efficacy
toxicity.
Unlike
host
genetics,
can
be
easily
modified
via
multiple
strategies,
faecal
transplantation
(FMT),
probiotics
antibiotics.
Preclinical
studies
have
identified
mechanisms
on
how
microbes
influence
treatment
outcomes.
Clinical
trials
also
demonstrated
potential
modulation
treatments.
Herein,
we
review
mechanistic
insights
microbial
interactions
with
chemotherapy
ICIs,
particularly
focusing
interplay
bacteria
pharmacokinetics
(eg,
metabolism,
enzymatic
degradation)
or
pharmacodynamics
immunomodulation)
treatment.
The
translational
basic
findings
clinical
settings
is
then
explored,
using
predictive
biomarkers
by
antibiotics,
probiotics,
prebiotics,
dietary
modulations
FMT.
We
further
discuss
current
patients
suggest
essential
directions
for
future
study.
era
personalised
medicine,
it
crucial
to
understand
its
cancer.
Manipulating
augment
responses
provide
new
into
Advanced Materials,
Год журнала:
2021,
Номер
33(38)
Опубликована: Авг. 4, 2021
Abstract
Bacteria
are
one
of
the
main
groups
organisms,
which
dynamically
and
closely
participate
in
human
health
disease
development.
With
integration
chemical
biotechnology,
bacteria
have
been
utilized
as
an
emerging
delivery
system
for
various
biomedical
applications.
Given
unique
features
such
their
intrinsic
biocompatibility
motility,
bacteria‐based
systems
drawn
wide
interest
diagnosis
treatment
diseases,
including
cancer,
infectious
kidney
failure,
hyperammonemia.
Notably,
at
interface
biotechnology
bacteria,
many
research
opportunities
initiated,
opening
a
promising
frontier
application.
Herein,
current
synergy
design
principles
systems,
microbial
modulation,
clinical
translation
reviewed,
with
special
focus
on
advances
therapy.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Май 13, 2023
Abstract
In
the
past
period,
due
to
rapid
development
of
next-generation
sequencing
technology,
accumulating
evidence
has
clarified
complex
role
human
microbiota
in
cancer
and
therapeutic
response.
More
importantly,
available
seems
indicate
that
modulating
composition
gut
improve
efficacy
anti-cancer
drugs
may
be
feasible.
However,
intricate
complexities
exist,
a
deep
comprehensive
understanding
how
interacts
with
is
critical
realize
its
full
potential
treatment.
The
purpose
this
review
summarize
initial
clues
on
molecular
mechanisms
regarding
mutual
effects
between
development,
highlight
relationship
microbes
immunotherapy,
chemotherapy,
radiation
therapy
surgery,
which
provide
insights
into
formulation
individualized
strategies
for
management.
addition,
current
emerging
microbial
interventions
as
well
their
clinical
applications
are
summarized.
Although
many
challenges
remain
now,
great
importance
cannot
overstated
strategies,
it
necessary
explore
holistic
approach
incorporates
modulation
cancer.
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.
