Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy
Cells,
Год журнала:
2024,
Номер
13(22), С. 1924 - 1924
Опубликована: Ноя. 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.
Язык: Английский
Hepatitis B virus induced cirrhosis and hepatocarcinoma: pathogenesis and therapeutics
Опубликована: Фев. 21, 2025
Hepatitis
B
virus
(HBV)
infection
is
a
major
risk
factor
of
cirrhosis
and
hepatocellular
carcinoma
(HCC)
worldwide.
Pathogenesis
HBV-induced
HCC
involves
viral
factors
virus-triggered
local
inflammatory
immune
responses,
the
latter
leading
to
progressive
fibrosis,
carcinogenesis.
Antiviral
therapeutics
suppress
HBV
replication
reduce
risks
HCC.
We
discuss
current
knowledge
on
pathogenesis
HCC,
focusing
mechanisms
emerging
antiviral
therapeutics.
Язык: Английский
New insights into T cell metabolism in liver cancer: from mechanism to therapy
Cell Death Discovery,
Год журнала:
2025,
Номер
11(1)
Опубликована: Март 23, 2025
Abstract
Liver
cancer
is
the
sixth
most
common
worldwide
and
third
cause
of
mortality.
The
development
progression
liver
metastases
a
multifaceted
process
involving
numerous
metabolic
pathways.
T
cells
have
protective
role
in
defense
against
cancer,
manipulating
pathways
can
alter
their
antitumor
activity.
Furthermore,
cell
nutrition
competition
lead
to
dysfunction
through
various
molecular
mechanisms.
Some
nanomaterials
drugs
improve
metabolism
promote
anti-liver
function
cells.
This
review
discusses
current
literature
regarding
changes
targeted
therapy
for
cancer.
promise
challenges
studying
target
treating
are
also
addressed.
Targeting
promising
approach
Язык: Английский
Current Advancements in Serum Protein Biomarkers for Hepatitis B Virus‐Associated Hepatocyte Remodeling and Hepatocellular Carcinoma
Immunity Inflammation and Disease,
Год журнала:
2025,
Номер
13(4)
Опубликована: Апрель 1, 2025
ABSTRACT
Background
Hepatitis
B
virus
(HBV)‐related
liver
cancer
is
the
third
most
common
cause
of
cancer‐related
death
globally.
Hepatocyte
remodeling,
also
known
as
hepatocyte
transformation
and
immortalization,
hepatocellular
carcinoma
(HCC),
are
brought
on
by
persistent
inflammation
caused
HBV
in
host
hepatocytes.
One
main
concerns
perspective
HBV‐induced
remodeling
accurately
identifying
stages
to
maximize
early
screening
detection.
Biological
signatures
have
a
significant
impact
solving
this
problem.
Objective
This
review
article
aimed
discuss
novel
serum
protein
biomarkers
for
HCC.
Methods
The
information
was
collected
from
various
peer‐reviewed
journals
through
electronic
searches
utilizing
search
engines,
including
PubMed,
Google
Scholar,
HINARI,
Cochrane
Library
2017
2024.
Keywords
included
“serum
HBV‐HCC,”
“blood‐based
“viral
HBV‐HCC.”
Results
Recently,
been
discovered
diagnosis,
treatment,
prognosis
hepatic
cell
HCC
proteomic
data
sets.
We
discussed
recent
literature
clinical
utility
diagnosis
forecasting
HBV‐associated
HCC,
golgi
73
(GP73),
glypican‐3
(GPC3),
midkine
(MDK),
des‐γ‐carboxy‐prothrombin
(DCP),
von
Willebrand
factor
(vWF),
pentraxin
3
(PTX3),
pseudouridine
synthases
7
(PUSs
7),
squamous
antigen
(SCCA),
osteopontin
(OPN).
Conclusion
All
these
markers
exhibit
survival
HBV‐related
patients,
proliferation,
migration,
antiapoptosis,
mitogenesis,
transformation,
angiogenesis
HBV‐infected
Язык: Английский
Manipulating the 4-1BB Pathway to Cure HBV
Infectious Diseases & Immunity,
Год журнала:
2024,
Номер
4(4), С. 156 - 157
Опубликована: Авг. 2, 2024
Chronic
Hepatitis
B
Virus
(HBV)
infection
is
a
major
global
health
issue
leading
to
liver
cirrhosis
and
hepatocellular
carcinoma.
Currently
available
treatments
have
limited
efficacy
in
completely
eradicating
the
virus.[1]
The
persistence
of
HBV
largely
due
virus's
ability
induce
dysfunctional
state
CD8+
T
cells.
One
critical
questions
why
HBV-specific
cells
become
how
this
dysfunction
can
be
reversed.[2,3]
It
hypothesized
that
co-signaling
receptors,
which
play
pivotal
role
cell
activation
regulation,
are
key
process.
Thus,
understanding
expression
modulation
these
receptors
may
help
identify
therapeutic
targets
restore
functionality
This
approach
based
on
observation
traditional
immune
checkpoint
inhibitors,
shown
success
other
chronic
infections
cancers,
minimal
impact
reversing
HBV-induced
dysfunction,[4]
therefore,
alternative
more
effective
context.
In
recent
study
by
Andreata
et
al,[4]
researchers
conducted
an
in-depth
analysis
receptor
address
their
infection.
utilized
combination
vivo
mouse
models,
bulk
single-cell
RNA
sequencing,
various
immunological
assays
upregulated
during
priming
examine
potential
as
targets.
While
blocking
co-inhibitory
such
PD-1,
CTLA-4,
LAG-3,
showed
efficacy,
co-stimulatory
4-1BB
OX40
significantly
restored
T-cell
function.
Specifically,
intrahepatically
primed
consisted
progenitor
or
stem-like
(TSL)
population
two
distinct
tissue-resident
memory
(TRM)
populations.
All
three
subsets
maintained
expression,
while
was
TSL.
agonism
highlighted
most
promising
strategy,
capable
converting
all
subpopulations
into
antiviral
effectors.
Finally,
patients
with
HBeAg+
CHB
infection,
rejuvenate
provides
detailed
exploration
molecular
mechanisms
underlying
demonstrates
activating
overcome
induced
thereby
restoring
activity.
primary
findings
abovementioned
experiments
monoclonal
lines
mice,
differ
from
polyclonal
responses
observed
at
stages
high
heterogeneity
quantity
functional
characteristics,
influenced
targeted
epitopes
patient's
disease
stage.
For
example,
were
rarely
detected
directly
ex
samples
levels
viremia.
Moreover,
Env-specific
T-cells
found
than
polymerase-
core-specific
T-cells.[5,6]
responsivity
interventions
also
varies.[7]
regulated
not
only
antigen
co-stimulation
but
cytokines
(such
IL-2)
metabolic
mechanisms.[8,9]
Therefore,
further
investigation
needed
understand
synergistic
interactions
among
signals,
cytokines,
factors.
conclusion,
compelling
evidence
targeting
effectively
offers
new
treatment
facilitated
development
new-generation
agonistic
drugs
improved
safety
tolerability.[10]
addition,
presents
target
for
optimizing
T-cell-based
strategies.
Funding
work
supported
National
Key
Research
Development
Program
China
(2022YFA1303600
2023YFC2308100)
Natural
Science
Foundation
(82130019).
Conflicts
Interest
None.
Editor
note:
Fu-Sheng
Wang
editor
Infectious
Diseases
&
Immunity.
article
subject
journal's
standard
procedures,
peer
review
handled
independently
his
research
group.
Язык: Английский
Viral Infections and the Glutathione Peroxidase Family: Mechanisms of Disease Development
Antioxidants and Redox Signaling,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 24, 2024
The
glutathione
peroxidase
(GPx)
family
is
recognized
for
its
essential
function
in
maintaining
cellular
redox
balance
and
countering
the
overproduction
of
reactive
oxygen
species
(ROS),
a
process
intricately
linked
to
progression
various
diseases
including
those
spurred
by
viral
infections.
modulation
GPx
activity
viruses
presents
critical
juncture
disease
pathogenesis,
influencing
responses
trajectory
infection-induced
diseases.
Язык: Английский
Single-cell analysis reveals distinct immune characteristics of hepatocellular carcinoma in HBV-positive versus HBV-negative cases
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 30, 2024
Abstract
Infection
with
the
Hepatitis
B
virus
(HBV)
is
a
key
risk
factor
for
Hepatocellular
carcinoma
(HCC)
development
and
progression.
It
widely
recognized
that
immunopathological
mechanisms
are
pivotal
in
developing
HBV-related
HCC.
Nevertheless,
specific
by
which
HBV-induced
modifications
within
tumor
microenvironment
(TME)
contribute
to
HCC
pathogenesis
still
not
well
understood.
Here,
we
utilized
single-cell
RNA
sequencing
analyze
compare
immune
landscapes
between
HBV-positive
HBV-negative
We
discovered
HBV
infection
significantly
modifies
cell
makeup
state,
leads
suppression
exhaustion
of
T
cells
TME.
Specifically,
an
increase
SLC4A10+
CD8+
IFITM3+
macrophages
was
observed,
along
upregulation
gene
SLC35F1
various
subtypes.
These
findings
offer
valuable
insights
into
alteration
immunological
associated
infection,
suggesting
possible
targets
immunotherapeutic
intervention.
Язык: Английский