Abstract
Cellular
proliferation,
function
and
survival
is
reliant
upon
maintaining
appropriate
intracellular
polyamine
levels.
Due
to
increased
metabolic
needs,
cancer
cells
elevate
their
pools
through
coordinated
metabolism
uptake.
High
levels
of
polyamines
have
been
linked
more
immunosuppressive
tumor
microenvironments
(TME)
as
support
the
growth
many
cell
types
such
MDSCs,
macrophages
regulatory
T-cells.
As
other
pro-tumorigenic
are
highly
dependent
on
for
survival,
pharmacological
modulation
a
promising
therapeutic
strategy.
This
review
covers
roles
in
various
TME
including
both
immune
stromal
cells,
well
how
competition
nutrients,
namely
precursors,
influences
cellular
landscape
TME.
It
also
details
use
biomarkers
ways
which
depletion
can
increase
immunogenicity
reprogram
tumors
become
responsive
immunotherapy.
Cell Communication and Signaling,
Год журнала:
2023,
Номер
21(1)
Опубликована: Дек. 4, 2023
Abstract
Polyamines
are
essential
for
the
growth
and
proliferation
of
mammalian
cells
intimately
involved
in
biological
mechanisms
such
as
DNA
replication,
RNA
transcription,
protein
synthesis,
post-translational
modification.
These
regulate
cellular
proliferation,
differentiation,
programmed
cell
death,
formation
tumors.
Several
studies
have
confirmed
positive
effect
polyamines
on
maintenance
health,
while
others
demonstrated
that
their
activity
may
promote
occurrence
progression
diseases.
This
review
examines
a
variety
topics,
polyamine
source
metabolism,
including
transport,
potential
impact
health
disease.
In
addition,
brief
summary
effects
oncogenes
signaling
pathways
tumor
metabolism
is
provided.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Окт. 18, 2024
Immunotherapy
has
made
significant
strides
in
cancer
treatment,
particularly
through
immune
checkpoint
blockade
(ICB),
which
shown
notable
clinical
benefits
across
various
tumor
types.
Despite
the
transformative
impact
of
ICB
treatment
therapy,
only
a
minority
patients
exhibit
positive
response
to
it.
In
with
solid
tumors,
those
who
respond
well
typically
demonstrate
an
active
profile
referred
as
"hot"
(immune-inflamed)
phenotype.
On
other
hand,
non-responsive
may
distinct
"cold"
(immune-desert)
phenotype,
differing
from
features
tumors.
Additionally,
there
is
more
nuanced
"excluded"
positioned
between
and
categories,
known
type.
Effective
differentiation
understanding
intrinsic
factors,
characteristics,
TME,
external
factors
are
critical
for
predicting
results.
It
widely
accepted
that
therapy
exerts
profound
effect
on
limited
efficacy
against
or
"altered"
necessitating
combinations
therapeutic
modalities
enhance
cell
infiltration
into
tissue
convert
tumors
ones.
Therefore,
aligning
traits
this
review
systematically
delineates
respective
influencing
extensively
discusses
varied
approaches
drug
targets
based
assess
efficacy.
Nature Genetics,
Год журнала:
2024,
Номер
56(3), С. 442 - 457
Опубликована: Фев. 15, 2024
Abstract
Clear
cell
renal
carcinoma
(ccRCC)
is
a
complex
disease
with
remarkable
immune
and
metabolic
heterogeneity.
Here
we
perform
genomic,
transcriptomic,
proteomic,
metabolomic
spatial
transcriptomic
analyses
on
100
patients
ccRCC
from
the
Tongji
Hospital
RCC
(TJ-RCC)
cohort.
Our
analysis
identifies
four
subtypes
including
De-clear
differentiated
(DCCD)-ccRCC,
subtype
distinctive
features.
DCCD
cancer
cells
are
characterized
by
fewer
lipid
droplets,
reduced
activity,
enhanced
nutrient
uptake
capability
high
proliferation
rate,
leading
to
poor
prognosis.
Using
single-cell
trajectory
analysis,
demonstrate
that
common
mode
of
progression.
Even
among
stage
I
patients,
associated
worse
outcomes
higher
recurrence
suggesting
it
cannot
be
cured
nephrectomy
alone.
study
also
suggests
treatment
strategy
based
subtype-specific
infiltration
could
guide
clinical
management
ccRCC.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Март 19, 2024
Abstract
Targeting
ferroptosis,
an
iron-dependent
form
of
regulated
cell
death
triggered
by
the
lethal
overload
lipid
peroxides,
in
cancer
therapy
is
impeded
our
limited
understanding
intersection
tumour’s
metabolic
feature
and
ferroptosis
vulnerability.
In
present
study,
arginine
identified
as
a
ferroptotic
promoter
using
metabolites
library.
This
effect
mainly
achieved
through
arginine’s
conversion
to
polyamines,
which
exerts
their
potent
ferroptosis-promoting
property
H
2
O
-dependent
manner.
Notably,
expression
ornithine
decarboxylase
1
(ODC1),
critical
enzyme
catalysing
polyamine
synthesis,
significantly
activated
signal——iron
overload——through
WNT/MYC
signalling,
well
subsequent
elevated
thus
forming
ferroptosis-iron
overload-WNT/MYC-ODC1-polyamine-H
positive
feedback
loop
that
amplifies
ferroptosis.
Meanwhile,
we
notice
cells
release
enhanced
polyamine-containing
extracellular
vesicles
into
microenvironment,
thereby
further
sensitizing
neighbouring
accelerating
“spread”
tumour
region.
Besides,
supplementation
also
sensitizes
or
xenograft
tumours
radiotherapy
chemotherapy
inducing
Considering
are
often
characterized
intracellular
pools,
results
indicate
metabolism
exposes
targetable
vulnerability
represents
exciting
opportunity
for
therapeutic
strategies
cancer.
Nature Cell Biology,
Год журнала:
2024,
Номер
26(9), С. 1571 - 1584
Опубликована: Авг. 8, 2024
Abstract
Caloric
restriction
and
intermittent
fasting
prolong
the
lifespan
healthspan
of
model
organisms
improve
human
health.
The
natural
polyamine
spermidine
has
been
similarly
linked
to
autophagy
enhancement,
geroprotection
reduced
incidence
cardiovascular
neurodegenerative
diseases
across
species
borders.
Here,
we
asked
whether
cellular
physiological
consequences
caloric
depend
on
metabolism.
We
report
that
levels
increased
upon
distinct
regimens
or
in
yeast,
flies,
mice
volunteers.
Genetic
pharmacological
blockade
endogenous
synthesis
fasting-induced
nematodes
cells.
Furthermore,
perturbing
pathway
vivo
abrogated
lifespan-
healthspan-extending
effects,
as
well
cardioprotective
anti-arthritic
fasting.
Mechanistically,
mediated
these
effects
via
induction
hypusination
translation
regulator
eIF5A.
In
summary,
polyamine–hypusination
axis
emerges
a
phylogenetically
conserved
metabolic
control
hub
for
fasting-mediated
enhancement
longevity.
Cell Reports,
Год журнала:
2024,
Номер
43(1), С. 113661 - 113661
Опубликована: Янв. 1, 2024
Myeloid-derived
suppressor
cells
(MDSCs)
impair
antitumor
immune
responses.
Identifying
regulatory
circuits
during
MDSC
development
may
bring
new
opportunities
for
therapeutic
interventions.
We
report
that
the
V-domain
of
T
cell
activation
(VISTA)
functions
as
a
key
enabler
differentiation.
VISTA
deficiency
reduced
STAT3
and
STAT3-dependent
production
polyamines,
which
causally
impaired
mitochondrial
respiration
expansion.
In
both
mixed
bone
marrow
(BM)
chimera
mice
myeloid-specific
conditional
knockout
mice,
significantly
tumor-associated
MDSCs
but
expanded
monocyte-derived
dendritic
(DCs)
enhanced
cell-mediated
tumor
control.
Correlated
expression
arginase-1
(ARG1),
enzyme
supporting
polyamine
biosynthesis,
was
observed
in
multiple
human
cancer
types.
endometrial
cancer,
co-expression
ARG1
on
myeloid
is
associated
with
poor
survival.
Taken
together,
these
findings
unveil
VISTA/polyamine
axis
central
regulator
differentiation
warrant
therapeutically
targeting
this
immunotherapy.
