Cells,
Journal Year:
2024,
Volume and Issue:
13(22), P. 1924 - 1924
Published: Nov. 20, 2024
Identifying
definitive
biomarkers
that
predict
clinical
response
and
resistance
to
immunotherapy
remains
a
critical
challenge.
One
emerging
factor
is
extracellular
acidosis
in
the
tumor
microenvironment
(TME),
which
significantly
impairs
immune
cell
function
contributes
failure.
However,
acidic
conditions
TME
disrupt
interaction
between
cancer
cells,
driving
tumor-infiltrating
T
cells
NK
into
an
inactivated,
anergic
state.
Simultaneously,
promotes
recruitment
activation
of
immunosuppressive
such
as
myeloid-derived
suppressor
regulatory
(Tregs).
Notably,
acidity
enhances
exosome
release
from
Tregs,
further
amplifying
immunosuppression.
Tumor
thus
acts
"protective
shield,"
neutralizing
anti-tumor
responses
transforming
pro-tumor
allies.
Therefore,
targeting
lactate
metabolism
has
emerged
promising
strategy
overcome
this
barrier,
with
approaches
including
buffer
agents
neutralize
pH
inhibitors
block
production
or
transport,
thereby
restoring
efficacy
TME.
Recent
discoveries
have
identified
genes
involved
(pHe)
regulation,
presenting
new
therapeutic
targets.
Moreover,
ongoing
research
aims
elucidate
molecular
mechanisms
acidification
develop
treatments
modulate
levels
enhance
outcomes.
Additionally,
future
studies
are
crucial
validate
safety
pHe-targeted
therapies
patients.
Thus,
review
explores
regulation
pHe
its
potential
role
improving
immunotherapy.
Advanced Science,
Journal Year:
2024,
Volume and Issue:
11(18)
Published: March 9, 2024
Abstract
Intrinsic
immunosuppressive
tumor
microenvironment
(ITM)
and
insufficient
infiltration
of
T
cells
severely
impede
the
progress
glioblastoma
(GBM)
immunotherapy.
In
this
study,
it
is
identify
that
inhibiting
expression
glucose
transporter
1
(GLUT1)
can
facilitate
prevention
lactate
excretion
from
glycolysis,
which
significantly
alleviates
lactate‐driven
ITM
by
reducing
tumor‐associated
macrophages
(TAMs)
regulatory
(Tregs).
Simultaneously,
findings
show
generated
inflammatory
cytokine
IFN‐γ
during
immune
activation
aggravates
escape
upregulating
checkpoint
programmed
death‐ligand
(PD‐L1)
in
TAMs.
Therefore,
an
injectable
thermogel
loaded
with
a
GLUT1
inhibitor
BAY‐876
PD‐1/PD‐L1
blocker
BMS‐1
(Gel@B‐B)
for
dual‐regulation
metabolism
immunity
GBM
developed.
Consequently,
situ
injection
Gel@B‐B
delays
growth
prolongs
survival
orthotopic
mouse
model.
By
actively
exposing
antigens
to
antigen‐presenting
cells,
vaccine
combined
found
increase
fraction
effector
(Th1/CTLs)
microenvironment,
thereby
remarkably
mitigating
recurrence
long‐term.
This
study
may
provide
promising
strategy
Acta Biochimica et Biophysica Sinica,
Journal Year:
2024,
Volume and Issue:
56(9), P. 1373 - 1386
Published: July 12, 2024
This
study
investigates
the
role
of
lactate
in
genesis
and
progression
ovarian
cancer
(OV)
explores
underlying
mechanisms.
Serum
levels
show
a
positive
correlation
with
tumor
grade
poor
prognosis
patients
OV.
Bioinformatics
analysis
identifies
CCL18
as
lactate-related
gene
CCL18
is
up-regulated
cancerous
tissues
positively
related
to
serum
OV
patients.
THP-1
cells
are
exposed
phorbol-12-myristate-13-acetate
for
M0
macrophage
induction.
The
results
RT-qPCR
ELISA
M1/M2
macrophage-related
markers
inflammatory
cytokines
that
exposure
macrophages
induces
M2
polarization.
Based
on
coculture
macrophages,
lactate-treated
significant
increase
proliferation
migration
cells.
However,
these
effects
can
be
reversed
by
silencing
Gpr132
or
treatment
anti-CCL18
antibody.
Experiments
using
xenograft
model
verify
oncogenic
growth
metastasis
relies
Gpr132
CCL18.
ChIP-qPCR
luciferase
reporter
assays
reveal
regulates
expression
via
H3K18
lactylation.
In
conclusion,
potential
therapeutic
target
It
involved
tumorigenesis
activating
lactylation
macrophages.
Biological reviews/Biological reviews of the Cambridge Philosophical Society,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 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.
The Journal of Immunology,
Journal Year:
2024,
Volume and Issue:
212(4), P. 723 - 736
Published: Jan. 10, 2024
Abstract
N
6-methyladenosine
(m6A)
is
the
most
abundant
mRNA
modification
in
mammals
and
it
plays
a
vital
role
various
biological
processes.
However,
roles
of
m6A
on
cervical
cancer
tumorigenesis,
especially
macrophages
infiltrated
tumor
microenvironment
cancer,
are
still
unclear.
We
analyzed
abnormal
methylation
using
CaSki
THP-1
cell
lines,
that
might
influence
macrophage
polarization
and/or
function
microenvironment.
In
addition,
C57BL/6J
BALB/c
nude
mice
were
used
for
validation
vivo.
this
study,
methylated
RNA
immunoprecipitation
sequencing
analysis
revealed
profiles
cancer.
Then,
we
discovered
high
expression
METTL14
(methyltransferase
14,
N6-adenosine-methyltransferase
subunit)
tissues
can
promote
proportion
programmed
death
protein
1
(PD-1)–positive
tumor-associated
macrophages,
which
have
an
obstacle
to
devour
cells.
Functionally,
changes
inhibit
recognition
phagocytosis
Mechanistically,
abnormality
could
target
glycolysis
tumors
vivo
vitro.
Moreover,
lactate
acid
produced
by
has
important
PD-1
as
proinflammatory
immunosuppressive
mediator.
effect
regulated
showed
was
potential
therapeutic
treating
advanced
human
cancers.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Aug. 29, 2024
Aging
is
characterized
by
chronic
systemic
inflammation
and
metabolic
changes.
We
compare
the
status
of
B
cells
from
young
elderly
donors
found
that
aging
associated
with
higher
oxygen
consumption
rates,
especially
extracellular
acidification
measures
oxidative
phosphorylation
anaerobic
glycolysis,
respectively.
Importantly,
this
status,
which
reflects
age-associated
expansion
pro-inflammatory
cells,
secretion
lactate
autoimmune
antibodies
after
in
vitro
stimulation.
individuals
induce
polarization
CD4+
T
into
through
pathways
mediated
lactate,
can
be
inhibited
targeting
enzymes
transporters,
as
well
signaling
supporting
glycolysis.
Lactate
also
induces
immunosenescent
are
glycolytic,
express
transcripts
for
multiple
molecules,
a
status.
These
results
altogether
may
have
relevant
clinical
implications
suggest
alternative
targets
therapeutic
interventions
patients
inflammatory
conditions
diseases.
Journal of Agricultural and Food Chemistry,
Journal Year:
2024,
Volume and Issue:
72(2), P. 1055 - 1066
Published: Jan. 3, 2024
In
addition
to
colorectal
cancer
and
metabolic
syndrome,
regular
yogurt
consumption
has
shown
promise
in
improving
skin
inflammation.
this
study,
we
investigated
the
effects
possible
mechanisms
of
on
imiquimod-induced
psoriasis-like
inflammation
mice.
After
oral
administration
with
(18
or
36
g/kg)
and/or
its
main
metabolite
lactate
(250
500
mg/kg)
for
3
days,
mice
were
treated
a
topical
dose
62.5
mg
imiquimod
(IMQ)
cream
seven
consecutive
days.
Data
showed
that
treatment
significantly
reduced
severity
lesions,
excessive
keratinocyte
proliferation,
immune
cell
infiltration.
Mechanistically,
found
genetic
deficiency
receptor
GPR81
aggravated
features
Activation
lactate/GPR81
axis
inhibited
degradation
IκBα,
prevented
nuclear
translocation
histone
deacetylase
(HDAC3)
macrophages,
thus
constrained
Overall,
these
findings
suggest
effectively
protects
against
experimental
psoriasis
targeting
signaling
could
be
promising
approach
management.
