Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Дек. 17, 2024
In
recent
years,
tumor
immunotherapy
has
become
an
active
research
area,
with
the
emergence
of
immune
checkpoint
inhibitors
(ICIs)
revolutionizing
immunotherapy.
Clinical
evidence
indicates
that
programmed
cell
death
protein
1
(PD-1)
monoclonal
antibodies
and
other
drugs
have
remarkable
therapeutic
effects.
V-domain
Ig
suppressor
T-cell
activation
(VISTA)
is
a
new
type
receptor
highly
expressed
in
various
tumors.
It
co-expressed
PD-1,
immunoglobulin
domain,
mucin
domain-3
(Tim-3),
immunoglobulin,
immunoreceptor
tyrosine-based
inhibitory
motif
domain
(TIGIT)
associated
prognosis,
which
suggests
it
may
be
target
for
As
no
mature
drugs,
VISTA
acute
myeloid
leukemia
(AML),
multiple
myeloma
(MM),
hematological
malignancies;
however,
its
pathogenic
mechanism
should
defined
to
better
guide
treatment.
Science Immunology,
Год журнала:
2024,
Номер
9(95)
Опубликована: Май 17, 2024
Immune
checkpoint
blockade
is
a
promising
approach
to
activate
antitumor
immunity
and
improve
the
survival
of
patients
with
cancer.
V-domain
immunoglobulin
suppressor
T
cell
activation
(VISTA)
an
immune
target;
however,
downstream
signaling
mechanisms
are
elusive.
Here,
we
identify
leucine-rich
repeats
immunoglobulin-like
domains
1
(LRIG1)
as
VISTA
binding
partner,
which
acts
inhibitory
receptor
by
engaging
suppressing
pathways.
Mice
cell-specific
LRIG1
deletion
developed
superior
responses
because
expansion
tumor-specific
cytotoxic
lymphocytes
(CTLs)
increased
effector
function
survival.
Sustained
tumor
control
was
associated
reduction
quiescent
CTLs
(TCF1
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 5, 2025
Summary
VISTA
is
a
key
immune
checkpoint
receptor
under
investigation
for
cancer
immunotherapy;
however,
its
signaling
mechanisms
remain
unclear.
Here
we
identify
conserved
four
amino
acid
(NPGF)
intracellular
motif
in
that
suppresses
cell
proliferation
by
constraining
cell-intrinsic
growth
signaling.
The
NPGF
binds
to
the
adapter
protein
NUMB
and
recruits
Rab11
endosomal
recycling
machinery.
We
characterize
class
of
triple-negative
breast
cancers
with
high
expression
low
proliferative
index.
In
tumor
cells
levels,
sequesters
at
endosomes,
which
interferes
epidermal
factor
(EGFR)
trafficking
suppress
growth.
These
effects
do
not
require
canonical
ligands,
nor
functioning
system.
As
consequence
expression,
EGFR
remains
abnormally
phosphorylated
cannot
propagate
ligand-induced
Mutation
domain
reverts
VISTA-induced
suppression
multiple
mouse
models.
results
define
mechanism
represses
control
malignant
epithelial
They
also
distinct
residues
are
critical
could
be
exploited
improve
immunotherapy.
Management
of
persistent
inflammation,
immunosuppression,
and
catabolism
syndrome
(PICS)
after
sepsis
remains
challenging
for
patients
in
the
intensive
care
unit,
experiencing
poor
quality
life
death.
However,
immune-cell
signatures
with
PICS
remain
unclear.
We
determined
at
single-cell
resolution.
Murine
cecal
ligation
puncture
models
were
applied
validation.
Immune
functions
two
enriched
monocyte
subpopulations,
Mono1
Mono4,
suppressed
substantially
partially
restored
exhibited
immunosuppressive
pro-apoptotic
effects
on
B
CD8T
cells.
Patients
had
reduced
naive
memory
cells
proliferated
plasma
Besides,
showed
an
active
antigen
processing
presentation
gene
signature
compared
to
those
sepsis.
better
prognoses
more
IGHA1-plasma
CD8TEMRA
displayed
signs
proliferation
immune
dysfunction
PICS-death
group
contrast
PICS-alive
group.
Megakaryocytes
was
pronounced
than
healthy
controls,
notable
changes
anti-inflammatory
immunomodulatory
observed
verified
mice
models.
Our
study
evaluated
level,
identifying
heterogeneity
present
within
subsets,
facilitating
prediction
disease
progression
development
effective
intervention.
This
work
supported
by
National
Natural
Science
Foundation
China,
Shanghai
Municipal
Health
Commission
"Yiyuan
New
Star"
Youth
Medical
Talent
Cultivating
Program,
Clinical
Research
Center
Anesthesiology.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 18, 2025
Growing
attention
has
been
directed
toward
the
critical
role
of
polyamines
in
tumor
microenvironment
and
immune
regulation.
Polyamines,
primarily
comprising
putrescine,
spermidine,
spermine,
are
tightly
regulated
through
coordinated
biosynthesis,
catabolism,
transport,
with
distinct
metabolic
patterns
between
normal
cancerous
tissues.
Emerging
evidence
highlights
pivotal
polyamine
metabolism
initiation,
progression,
metastasis.
This
review
aims
to
elucidate
differences
catabolism
tissues,
as
well
associated
alterations
epigenetic
modifications
resistance
checkpoint
blockade
driven
by
metabolism.
Polyamine
influences
both
cells
modulating
cell
phenotypes-shifting
them
towards
either
suppression
or
evasion
within
microenvironment.
Additionally,
impacts
immunotherapy
its
regulation
key
enzymes.
also
explores
potential
therapeutic
targets
summarizes
roles
inhibitors
combination
for
cancer
treatment,
offering
a
novel
perspective
on
strategies.
Journal of Clinical Investigation,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 2, 2025
Type-2
innate
lymphoid
cells
(ILC2s)
play
a
pivotal
role
in
the
development
of
airway
hyperreactivity
(AHR).
However,
regulatory
mechanisms
governing
ILC2
function
remain
inadequately
explored.
This
study
uncovers
V-domain
Ig
suppressor
T
cell
activation
(VISTA)
as
an
inhibitory
immune
checkpoint
crucial
for
modulating
ILC2-driven
lung
inflammation.
VISTA
is
upregulated
activated
pulmonary
ILC2s
and
plays
key
regulating
inflammation,
VISTA-deficient
demonstrate
increased
proliferation
function,
resulting
elevated
type-2
cytokine
production
exacerbation
AHR.
Mechanistically,
stimulation
activates
Forkhead
box
O1
(FOXO1),
leading
to
modulation
function.
The
suppressive
effects
FOXO1
on
effector
were
confirmed
using
inhibitors
activators.
Moreover,
exhibit
enhanced
fatty
acid
oxidation
oxidative
phosphorylation
meet
their
high
energy
demands.
Therapeutically,
agonist
treatment
reduces
both
ex
vivo
vivo,
significantly
alleviating
Our
murine
findings
validated
human
ILC2s,
where
humanized
mouse
model
studies
unravel
regulation
via
pathway,
presenting
potential
therapeutic
strategies
allergic
asthma
by
responses.
Molecular Medicine,
Год журнала:
2025,
Номер
31(1)
Опубликована: Фев. 4, 2025
Abstract
Amino
acids
are
pivotal
regulators
of
immune
cell
metabolism,
signaling
pathways,
and
gene
expression.
In
myeloid
cells,
these
processes
underlie
their
functional
plasticity,
enabling
shifts
between
pro-inflammatory,
anti-inflammatory,
pro-tumor,
anti-tumor
activities.
Within
the
tumor
microenvironment,
amino
acid
metabolism
plays
a
crucial
role
in
mediating
immunosuppressive
functions
contributing
to
progression.
This
review
delves
into
mechanisms
by
which
specific
acids—glutamine,
serine,
arginine,
tryptophan—regulate
function
polarization.
Furthermore,
we
explore
therapeutic
potential
targeting
enhance
immunity,
offering
insights
novel
strategies
for
cancer
treatment.
Acta Biochimica et Biophysica Sinica,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 1, 2025
The
dysregulation
of
polyamines
in
tumors
has
made
polyamine
metabolism
an
appealing
target
for
cancer
therapy.
Gene
mutations
drive
the
reprogramming
tumors,
presenting
promising
opportunities
clinical
treatment.
proposed
strategies
involve
inhibiting
biosynthesis
while
also
targeting
transport
system
as
antitumor
approaches.
A
growing
number
drugs
aimed
at
and
systems
are
undergoing
trials.
Polyamine
plays
a
role
regulating
signaling
pathways,
suggesting
potential
combination
therapies
Furthermore,
supplemental
substances
have
demonstrated
activity,
indicating
that
combining
with
downstream
targets
or
immunotherapy
could
offer
significant
benefits.
These
discoveries
open
new
avenues
leveraging
anticancer
