Theranostics,
Год журнала:
2025,
Номер
15(6), С. 2338 - 2359
Опубликована: Янв. 13, 2025
Rationale:
Tumor
cells
possess
sophisticated
strategies
to
circumvent
immune
detection,
including
the
modulation
of
endogenous
checkpoints,
particularly
those
within
B7
family.
Elucidating
mechanisms
that
govern
induction
family
molecules
is
crucial
for
advancement
immunotherapy.
Lysine
lactylation
(Kla),
a
newly
identified
epigenetic
modification,
suggested
may
play
role
in
reshaping
tumor
microenvironment
and
facilitating
evasion.
Methods:
We
analyzed
glycolysis
pathway's
enrichment
patients
with
immune-evading
tumors
assessed
impact
lactate
treatment
on
antitumor
immunity
CD8+
T
microenvironment.
interrupted
using
dehydrogenase
A
(LDHA)
knockdown
sodium
oxamate,
evaluated
its
effects
cell
cytotoxicity.
Additionally,
we
investigated
correlation
between
B7-H3
expression
pathway,
explored
molecular
underlying
lactate-induced
expression.
Results:
Our
findings
revealed
pathway
was
highly
enriched
tumors.
Lactate
inhibited
cells,
whereas
interruption
via
LDHA
or
oxamate
augmented
cytotoxicity
effectively
counteracting
found
be
closely
linked
pathway.
Mechanistically,
lactate-upregulated
H3K18la
directly
bound
promoter
conjunction
transcription
factor
Creb1
co-activator
Ep300,
leading
increased
contributing
progression
by
compromising
proportion
tumor-infiltrating
cells.
In
mouse
bearing
models,
inhibiting
suppressed
growth,
activated
demonstrated
potent
anti-tumor
efficacy.
Furthermore,
this
approach
enhanced
efficacy
anti-PD-1
treatment.
Conclusions:
This
study
uncovers
novel
mechanism
which
modulates
through
expression,
providing
new
avenues
metabolism-targeted
Biological reviews/Biological reviews of the Cambridge Philosophical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 16, 2024
ABSTRACT
In
recent
years,
a
significant
breakthrough
has
emerged
in
biology,
the
identification
of
lactylation,
novel
post‐translational
process.
This
intriguing
modification
is
not
limited
to
specific
class
proteins
but
occurs
across
diverse
range,
including
histones,
signalling
molecules,
enzymes,
and
substrates.
It
can
exert
broad
regulatory
role
various
diseases,
ranging
from
developmental
anomalies
neurodegenerative
disorders
inflammation
cancer.
Thus,
it
presents
exciting
opportunities
for
exploring
innovative
treatment
approaches.
As
result,
there
been
surge
research
interest,
leading
deeper
understanding
molecular
mechanisms
functions
underlying
lactylation
within
physiological
pathological
processes.
Here,
we
review
detection
biological
disease
effects,
providing
systematic
overview
this
modification.
Clinical Science,
Год журнала:
2025,
Номер
139(02), С. 151 - 169
Опубликована: Янв. 1, 2025
Lactylation,
a
post-translational
modification,
has
been
linked
to
gene
transcription
regulation
through
epigenetic
modulation
in
various
pathophysiological
processes.
The
lactylation
regulatory
proteins,
known
as
writers,
erasers,
and
readers,
govern
their
dynamics
by
adding,
removing,
recognizing
lactyl
groups
on
proteins.
Macrophages,
cells
of
the
immune
system,
maintain
homeostasis,
responding
dynamically
diverse
internal
external
stimuli.
Emerging
researches
unveil
that
lactylation,
inducing
macrophage
activation
polarization,
affects
functionality
pathological
conditions
such
inflammation,
tumor
microenvironment,
fibrosis.
Evidence
progressively
indicates
lactate-driven
alterations
levels
within
macrophages
can
influence
pathogenesis
numerous
diseases.
This
review
aims
systematically
summarize
research
progress
macrophages,
explore
its
functions
mechanisms
which
contributes
pathology
different
disease
phenotypes,
propose
future
directions
along
with
potential
diagnostic
therapeutic
strategies.
Theranostics,
Год журнала:
2025,
Номер
15(6), С. 2338 - 2359
Опубликована: Янв. 13, 2025
Rationale:
Tumor
cells
possess
sophisticated
strategies
to
circumvent
immune
detection,
including
the
modulation
of
endogenous
checkpoints,
particularly
those
within
B7
family.
Elucidating
mechanisms
that
govern
induction
family
molecules
is
crucial
for
advancement
immunotherapy.
Lysine
lactylation
(Kla),
a
newly
identified
epigenetic
modification,
suggested
may
play
role
in
reshaping
tumor
microenvironment
and
facilitating
evasion.
Methods:
We
analyzed
glycolysis
pathway's
enrichment
patients
with
immune-evading
tumors
assessed
impact
lactate
treatment
on
antitumor
immunity
CD8+
T
microenvironment.
interrupted
using
dehydrogenase
A
(LDHA)
knockdown
sodium
oxamate,
evaluated
its
effects
cell
cytotoxicity.
Additionally,
we
investigated
correlation
between
B7-H3
expression
pathway,
explored
molecular
underlying
lactate-induced
expression.
Results:
Our
findings
revealed
pathway
was
highly
enriched
tumors.
Lactate
inhibited
cells,
whereas
interruption
via
LDHA
or
oxamate
augmented
cytotoxicity
effectively
counteracting
found
be
closely
linked
pathway.
Mechanistically,
lactate-upregulated
H3K18la
directly
bound
promoter
conjunction
transcription
factor
Creb1
co-activator
Ep300,
leading
increased
contributing
progression
by
compromising
proportion
tumor-infiltrating
cells.
In
mouse
bearing
models,
inhibiting
suppressed
growth,
activated
demonstrated
potent
anti-tumor
efficacy.
Furthermore,
this
approach
enhanced
efficacy
anti-PD-1
treatment.
Conclusions:
This
study
uncovers
novel
mechanism
which
modulates
through
expression,
providing
new
avenues
metabolism-targeted
