Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: May 13, 2025
The
tumor
microenvironment
(TME)
is
characterized
by
distinct
metabolic
adaptations
that
not
only
drive
progression
but
also
profoundly
influence
immune
responses.
Among
these
adaptations,
lactate,
a
key
byproduct
of
aerobic
glycolysis,
accumulates
in
the
TME
and
plays
pivotal
role
regulating
cellular
metabolism
cell
function.
Tumor-associated
macrophages
(TAMs),
known
for
their
remarkable
functional
plasticity,
serve
as
critical
regulators
progression.
Lactate
modulates
TAM
polarization
influencing
M1/M2
phenotypic
balance
through
diverse
signaling
pathways,
while
simultaneously
driving
reprogramming.
Furthermore,
lactate-mediated
histone
protein
lactylation
reshapes
gene
expression,
reinforcing
immunosuppressive
properties.
From
therapeutic
perspective,
targeting
lactate
has
shown
promise
reprogramming
TAMs
enhancing
anti-tumor
immunity.
Combining
interventions
with
immunotherapies
may
further
augment
treatment
efficacy.
This
review
underscores
crucial
regulation
progression,
highlighting
its
potential
promising
target
cancer
treatment.
Cellular and Molecular Immunology,
Journal Year:
2024,
Volume and Issue:
21(12), P. 1376 - 1409
Published: Nov. 8, 2024
АBSTRACT:
With
increasing
incidence
and
geography,
cancer
is
one
of
the
leading
causes
death,
reduced
quality
life
disability
worldwide.
Principal
progress
in
development
new
anticancer
therapies,
improving
efficiency
immunotherapeutic
tools,
personification
conventional
therapies
needs
to
consider
cancer-specific
patient-specific
programming
innate
immunity.
Intratumoral
TAMs
their
precursors,
resident
macrophages
monocytes,
are
principal
regulators
tumor
progression
therapy
resistance.
Our
review
summarizes
accumulated
evidence
for
subpopulations
number
biomarkers,
indicating
predictive
value
clinical
parameters
carcinogenesis
resistance,
with
a
focus
on
solid
cancers
non-infectious
etiology.
We
present
state-of-the-art
knowledge
about
tumor-supporting
functions
at
all
stages
highlight
recently
identified
by
single-cell
spatial
analytical
methods,
that
discriminate
between
tumor-promoting
tumor-inhibiting
TAMs,
where
both
subtypes
express
combination
prototype
M1
M2
genes.
focuses
novel
mechanisms
involved
crosstalk
among
epigenetic,
signaling,
transcriptional
metabolic
pathways
TAMs.
Particular
attention
has
been
given
link
cell
metabolism
epigenetic
histone
lactylation,
which
can
be
responsible
unlimited
protumoral
Finally,
we
explain
how
interfere
currently
used
therapeutics
summarize
most
advanced
data
from
trials,
divide
into
four
categories:
inhibition
TAM
survival
differentiation,
monocyte/TAM
recruitment
tumors,
functional
reprogramming
genetic
enhancement
macrophages.
Signal Transduction and Targeted Therapy,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: Feb. 11, 2025
Abstract
Accumulated
evidence
has
implicated
the
diverse
and
substantial
influence
of
lactate
on
cellular
differentiation
fate
regulation
in
physiological
pathological
settings,
particularly
intricate
conditions
such
as
cancer.
Specifically,
been
demonstrated
to
be
pivotal
molding
tumor
microenvironment
(TME)
through
its
effects
different
cell
populations.
Within
cells,
impacts
signaling
pathways,
augments
shuttle
process,
boosts
resistance
oxidative
stress,
contributes
lactylation.
In
various
populations,
interplay
between
immune
cells
governs
processes
differentiation,
response,
surveillance,
treatment
effectiveness.
Furthermore,
communication
stromal/endothelial
supports
basal
membrane
(BM)
remodeling,
epithelial-mesenchymal
transitions
(EMT),
metabolic
reprogramming,
angiogenesis,
drug
resistance.
Focusing
production
transport,
specifically
dehydrogenase
(LDH)
monocarboxylate
transporters
(MCT),
shown
promise
Inhibitors
targeting
LDH
MCT
act
both
suppressors
enhancers
immunotherapy,
leading
a
synergistic
therapeutic
effect
when
combined
with
immunotherapy.
The
review
underscores
importance
progression
provides
valuable
perspectives
potential
approaches
that
target
vulnerability
metabolism,
highlighting
Heel
Achilles
for
cancer
treatment.
Cell Death Discovery,
Journal Year:
2025,
Volume and Issue:
11(1)
Published: Feb. 8, 2025
Abstract
Histone
lactylation
plays
a
crucial
role
in
cancer
progression,
but
its
impact
on
breast
(BC)
tumorigenesis
is
still
unclear.
We
utilized
chromatin
immunoprecipitation
sequencing
with
H3K18la
antibodies,
transcriptomics
of
clinical
BC
samples,
and
proteomics
ATAC-seq
analyses
vivo
tumors
to
identify
the
genes
regulated
by
transcription
factor
PPARD.
qPCR
Western
blot
assays
were
used
detect
expressions
molecules.
discovered
that
levels
higher
tissues
compared
adjacent
non-cancerous
tissues.
promoted
expression
PPARD,
which
turn
influenced
AKT,
not
ILK.
analysis
revealed
glycolysis
cells
enhanced
accessibility.
Additionally,
we
confirmed
HDAC2
HDAC3
act
as
“erasers”
for
H3
lysine
lactylation.
During
analysis,
AKT-phosphorylation
aerobic
respiration
inhibitor
group
exhibited
an
apparent
disparity
activity.
Our
study
demonstrated
changes
downstream
PPARD
support
cell
survival
under
anaerobic
conditions.
accelerated
proliferation
promoting
phosphorylation
AKT.
This
highlights
therapeutic
potential
targeting
H3K18la/PPARD/AKT
axis
cancer,
providing
new
insights
into
epigenetic
regulation
metabolism
(Trial
registration:
The
was
approved
Research
Ethics
Committee
Shandong
Provincial
Third
Hospital
(KYLL-2023057;
https://www.medicalresearch.org.cn/
)).
Theranostics,
Journal Year:
2025,
Volume and Issue:
15(5), P. 1787 - 1821
Published: Jan. 2, 2025
Lactate
is
an
indispensable
substance
in
various
cellular
physiological
functions
and
plays
regulatory
roles
different
aspects
of
energy
metabolism
signal
transduction.
Lactylation
(Kla),
a
key
pathway
through
which
lactate
exerts
its
functions,
has
been
identified
as
novel
posttranslational
modification
(PTM).
Research
indicates
that
Kla
essential
balancing
mechanism
variety
organisms
involved
many
biological
processes
pathways.
closely
related
to
disease
development
represents
potential
important
new
drug
target.
In
line
with
existing
reports,
we
searched
for
newly
discovered
sites
on
histone
nonhistone
proteins;
reviewed
the
mechanisms
(particularly
focusing
enzymes
directly
reversible
regulation
Kla,
including
"writers"
(modifying
enzymes),
"readers"
(modification-binding
"erasers"
(demodifying
enzymes);
summarized
crosstalk
between
PTMs
help
researchers
better
understand
widespread
distribution
diverse
functions.
Furthermore,
considering
"double-edged
sword"
role
both
pathological
contexts,
this
review
highlights
"beneficial"
states
(energy
metabolism,
inflammatory
responses,
cell
fate
determination,
development,
etc.)
"detrimental"
pathogenic
or
inducive
effects
processes,
particularly
malignant
tumors
complex
nontumor
diseases.
We
also
clarify
molecular
health
disease,
discuss
feasibility
therapeutic
Finally,
describe
detection
technologies
their
applications
diagnosis
clinical
settings,
aiming
provide
insights
treatment
diseases
accelerate
translation
from
laboratory
research
practice.
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
15
Published: Jan. 10, 2025
Lactate,
long
viewed
as
a
byproduct
of
glycolysis
and
metabolic
waste.
Initially
identified
within
the
context
yogurt
fermentation,
lactate's
role
extends
beyond
culinary
applications
to
its
significance
in
biochemical
processes.
Contemporary
research
reveals
that
lactate
functions
not
merely
terminal
product
but
also
nexus
for
initiating
physiological
pathological
responses
body.
Lysine
lactylation
(Kla),
novel
post-translational
modification
(PTM)
proteins,
has
emerged
pivotal
mechanism
by
which
exerts
regulatory
influence.
This
epigenetic
potential
alter
gene
expression
patterns,
thereby
impacting
Increasing
evidence
indicates
correlation
between
adverse
prognosis
various
malignancies.
Consequently,
this
review
article
aims
encapsulate
proteins
interact
with
lactate,
elucidate
tumorigenesis
progression,
explore
therapeutic
targets
afforded
modulation
lactylation.
The
objective
is
clarify
oncogenic
provide
strategic
framework
future
directions
burgeoning
field.
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: Feb. 28, 2025
Objective
Ovarian
cancer
(OC)
ranks
among
the
foremost
causes
of
mortality
in
gynecological
malignancies,
with
chemoresistance
being
primary
factor
contributing
to
unfavorable
prognosis.
This
work
seeks
clarify
mechanisms
resistance-related
lactylation
OC,
intending
offer
novel
theoretical
foundations
and
therapy
strategies
for
addressing
chemoresistance.
Methods
Through
combined
analysis
bulk
RNA-seq
single-cell
data,
we
initially
found
genes
linked
Subsequently,
employed
differential
expression
analysis,
survival
enrichment
other
methodologies
further
investigate
roles
molecular
these
tumor
resistance.
Ultimately,
investigated
resistant
non-resistant
tissues
cells
via
experimentation.
Results
We
two
candidate
associated
chemoresistance,
ALDH1A1
S100A4.
Analysis
data
indicated
that
represent
cell
subpopulation
relevant
resistance
studies.
Subpopulation
several
subtypes
were
markedly
resistance,
elevated
levels
S100A4
subpopulation,
notably
correlating
various
immunological
metabolic
pathways.
pathways
oxidative
phosphorylation
glycolysis
activity
was
lactic
acid
buildup
The
investigation
marker
gene
protein-protein
interaction
network
subgroup
elucidated
intricate
interactions
genes.
OC
platinum-resistant
cohort
compared
sensitive
cohort,
a
considerable
rise
observed
cells,
demonstrating
co-localization
lactylation.
Conclusion
elucidates
significant
function
identifies
as
possible
drug
These
findings
enhance
our
comprehension
behind
critical
insights
formulation
therapeutic
options.
Experimental Hematology and Oncology,
Journal Year:
2025,
Volume and Issue:
14(1)
Published: March 8, 2025
Cancer
remains
the
leading
cause
of
mortality
worldwide,
and
emergence
drug
resistance
has
made
identification
new
therapeutic
targets
imperative.
Lactate,
traditionally
viewed
as
a
byproduct
glycolysis
with
limited
ATP-producing
capacity,
recently
gained
recognition
critical
signaling
molecule.
It
plays
key
role
not
only
in
cancer
cell
metabolism
but
also
shaping
tumor
microenvironment
(TME).
Histone
lysine
lactylation,
newly
identified
post-translational
modification,
been
shown
to
influence
range
cellular
processes
cancer.
Current
research
focuses
on
mechanisms
functions
histone
lactylation
cancer,
including
its
gene
expression
regulation,
signal
transduction,
protein
synthesis.
However,
despite
these
advancements,
there
are
still
plenty
barriers
quest
unravel
modification.
The
single-cell
spatial
transcriptomics
may
offer
valuable
insights
for
selecting
targets.
This
review
provides
comprehensive
summary
applications
modification
clinical
settings.
Through
detailed
analysis,
we
identify
challenges
limitations
that
exist
current
landscape.
These
lay
groundwork
future
studies
by
highlighting
promising
directions.
Frontiers in Oncology,
Journal Year:
2025,
Volume and Issue:
15
Published: March 19, 2025
Lactylation
modifications
have
been
shown
to
be
a
novel
type
of
protein
post-translational
(PTMs),
providing
new
perspective
for
understanding
the
interaction
between
cellular
metabolic
reprogramming
and
epigenetic
regulation.
Studies
that
lactylation
plays
an
important
role
in
occurrence,
development,
angiogenesis,
invasion
metastasis
tumors.
It
can
not
only
regulate
phenotypic
expression
functional
polarization
immune
cells,
but
also
participate
formation
tumor
drug
resistance
through
variety
molecular
mechanisms.
In
this
review,
we
review
latest
research
progress
modification
tumors,
focusing
on
its
mechanism
action
cell
regulation
microenvironment
(TME),
resistance,
aiming
provide
theoretical
basis
ideas
discovery
therapeutic
targets
methods.
Through
in-depth
analysis
modification,
it
is
expected
open
up
direction
treatment
potential
strategies
overcoming
improving
clinical
efficacy.
