Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: Aug. 11, 2020
Abstract
Tryptophan
catabolism
by
the
enzymes
indoleamine
2,3-dioxygenase
1
and
tryptophan
2
(IDO/TDO)
promotes
immunosuppression
across
different
cancer
types.
The
metabolite
L-Kynurenine
(Kyn)
interacts
with
ligand-activated
transcription
factor
aryl
hydrocarbon
receptor
(AHR)
to
drive
generation
of
Tregs
tolerogenic
myeloid
cells
PD-1
up-regulation
in
CD8
+
T
cells.
Here,
we
show
that
AHR
pathway
is
selectively
active
IDO/TDO-overexpressing
tumors
associated
resistance
immune
checkpoint
inhibitors.
We
demonstrate
IDO-Kyn-AHR-mediated
depends
on
an
interplay
between
tumor-associated
macrophages,
which
can
be
reversed
inhibition.
Selective
blockade
delays
progression
tumors,
its
efficacy
improved
combination
blockade.
Our
findings
suggest
blocking
IDO/TDO
expressing
would
overcome
limitation
single
IDO
or
TDO
targeting
agents
constitutes
a
personalized
approach
immunotherapy,
particularly
Nutrients,
Journal Year:
2019,
Volume and Issue:
11(4), P. 923 - 923
Published: April 24, 2019
The
gut
microbiota
is
a
highly
complex
community
which
evolves
and
adapts
to
its
host
over
lifetime.
It
has
been
described
as
virtual
organ
owing
the
myriad
of
functions
it
performs,
including
production
bioactive
metabolites,
regulation
immunity,
energy
homeostasis
protection
against
pathogens.
These
activities
are
dependent
on
quantity
quality
alongside
metabolic
potential,
dictated
by
number
factors,
diet
genetics.
In
this
regard,
microbiome
malleable
varies
significantly
from
host.
two
features
render
candidate
‘organ’
for
possibility
precision
microbiomics—the
use
biomarker
predict
responsiveness
specific
dietary
constituents
generate
diets
interventions
optimal
health.
With
in
mind,
two-part
review
investigates
current
state
science
terms
influence
components
subsequent
consequences
health
status,
along
with
opportunities
modulate
improved
potential
components.
particular,
Part
I,
we
examine
development
birth
role
We
investigate
poor-quality
relation
infection
inflammation
discuss
diet-derived
microbial
metabolites
negatively
impact
look
at
shaping
components,
namely
protein,
fat
carbohydrates,
composition.
Nutrients,
Journal Year:
2021,
Volume and Issue:
13(2), P. 699 - 699
Published: Feb. 22, 2021
The
most
prevalent
diseases
of
our
time,
non-communicable
(NCDs)
(including
obesity,
type
2
diabetes,
cardiovascular
and
some
types
cancer)
are
rising
worldwide.
All
them
share
the
condition
an
“inflammatory
disorder”,
with
impaired
immune
functions
frequently
caused
or
accompanied
by
alterations
in
gut
microbiota.
These
multifactorial
maladies
also
have
common
malnutrition
related
to
physiopathology.
In
this
context,
diet
is
greatest
modulator
system–microbiota
crosstalk,
much
interest,
new
challenges,
arising
area
precision
nutrition
as
a
way
towards
treatment
prevention.
It
fact
that
westernized
(WD)
partly
responsible
for
increased
prevalence
NCDs,
negatively
affecting
both
microbiota
system.
Conversely,
other
nutritional
approaches,
such
Mediterranean
(MD),
positively
influence
system
microbiota,
proposed
not
only
potential
tool
clinical
management
different
disease
conditions,
but
prevention
health
promotion
globally.
Thus,
purpose
review
determine
regulatory
role
components
WD
MD
interplay,
order
understand,
create
awareness
of,
over
key
components.
British Journal of Cancer,
Journal Year:
2019,
Volume and Issue:
122(1), P. 30 - 44
Published: Dec. 10, 2019
Abstract
Based
on
its
effects
both
tumour
cell
intrinsic
malignant
properties
as
well
anti-tumour
immune
responses,
tryptophan
catabolism
has
emerged
an
important
metabolic
regulator
of
cancer
progression.
Three
enzymes,
indoleamine-2,3-dioxygenase
1
and
2
(IDO1/2)
tryptophan-2,3-dioxygenase
(TDO2),
catalyse
the
first
step
degradation
essential
amino
acid
(Trp)
to
kynurenine
(Kyn).
The
notion
inhibiting
IDO1
using
small-molecule
inhibitors
elicited
high
hopes
a
positive
impact
in
field
immuno-oncology,
by
restoring
responses
synergising
with
other
immunotherapies
such
checkpoint
inhibition.
However,
clinical
trials
have
yielded
disappointing
results,
hence
raising
many
questions.
This
review
will
discuss
strategies
target
Trp-degrading
enzymes
possible
down-stream
consequences
their
We
aim
provide
comprehensive
background
information
Trp
catabolic
targets
immuno-oncology
current
state
development.
Details
inhibitors,
including
patient
stratification,
themselves,
pre-treatments
therapies
were
combined
with,
are
discussed
mechanisms
proposed
that
might
compensated
for
Finally,
alternative
approaches
suggested
circumvent
these
problems.
