Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Май 1, 2025
Histone
modifications,
including
methylation,
acetylation,
lactylation,
phosphorylation,
ubiquitination,
SUMOylation,
ADP-ribosylation,
and
crotonylation,
critically
regulate
tumor-associated
macrophages
(TAMs)
polarization
by
modulating
gene
expression
functional
states.
Reprogramming
TAMs
from
M2
to
M1
phenotypes
through
epigenetic
targeting
has
emerged
as
a
promising
strategy
enhance
anti-tumor
immunity
improve
the
efficacy
of
cancer
immunotherapy.
This
review
explores
role
histone
modifications
in
TAM
biology,
their
interplay
with
metabolic
reprogramming,
opportunities
challenges
developing
epigenetic-based
therapies
advance
Molecular Medicine,
Год журнала:
2025,
Номер
31(1)
Опубликована: Апрель 22, 2025
Abstract
In
the
clinical
management
of
cancers,
emergence
chemoresistance
represents
a
profound
and
imperative
“pain
point”
that
requires
immediate
attention.
Understanding
mechanisms
is
essential
for
developing
effective
therapeutic
strategies.
Importantly,
existing
studies
have
demonstrated
glucose
metabolic
reprogramming,
commonly
referred
to
as
Warburg
effect
or
aerobic
glycolysis,
major
contributor
chemoresistance.
Additionally,
lactate,
byproduct
functions
signaling
molecule
supports
lysine
lactylation
modification
proteins,
which
also
plays
critical
role
in
However,
it
insufficient
discuss
glycolysis
from
single
perspective.
The
intricate
relationship
between
crucial
promoting
Thus,
thorough
elucidation
underlying
mediated
by
essential.
This
review
provides
comprehensive
overview
these
further
outlines
exert
synergistic
effects,
development
creating
positive
feedback
loop
continues
mediate
this
resistance.
close
link
suggests
application
glycolysis-related
drugs
inhibitors
cancer
therapy
may
represent
promising
anticancer
strategy.
Furthermore,
targeted
lactylation,
either
alone
combination
with
other
treatments,
offer
new
avenues
overcoming
Cell Death Discovery,
Год журнала:
2025,
Номер
11(1)
Опубликована: Апрель 30, 2025
Lactate,
the
end
product
of
glycolysis,
plays
a
crucial
role
in
cellular
signaling
and
metabolism.
The
discovery
lactylation,
novel
post-translational
modification,
has
uncovered
lactate
regulating
diseases,
especially
brain.
Lactylation
connects
genetic
encoding
with
protein
function,
thereby
influencing
key
biological
processes.
Increasing
evidence
supports
lactate-mediated
lactylation
as
critical
modulator
neurological
disorders.
This
review
offers
an
overview
metabolism
highlighting
recent
advances
understanding
regulatory
enzymes
their
central
nervous
system.
We
investigate
impact
on
brain
dysfunctions,
including
neurodegenerative
cerebrovascular
disorders,
neuroinflammation,
tumors,
psychiatric
conditions.
Moreover,
we
highlight
therapeutic
potential
targeting
treating
disorders
outline
research
gaps
future
directions
needed
to
advance
this
promising
field.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Май 1, 2025
Histone
modifications,
including
methylation,
acetylation,
lactylation,
phosphorylation,
ubiquitination,
SUMOylation,
ADP-ribosylation,
and
crotonylation,
critically
regulate
tumor-associated
macrophages
(TAMs)
polarization
by
modulating
gene
expression
functional
states.
Reprogramming
TAMs
from
M2
to
M1
phenotypes
through
epigenetic
targeting
has
emerged
as
a
promising
strategy
enhance
anti-tumor
immunity
improve
the
efficacy
of
cancer
immunotherapy.
This
review
explores
role
histone
modifications
in
TAM
biology,
their
interplay
with
metabolic
reprogramming,
opportunities
challenges
developing
epigenetic-based
therapies
advance
