Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 8, 2024
Abstract
Objective:
This
study
aimed
to
investigate
the
causal
relationship
between
inflammatory
cytokines
and
oral
cavity
cancer
risk
using
Mendelian
randomization
analysis.
Methods:
Two-sample
was
conducted
summary-level
genome-wide
association
data
on
41
in
Europeans.
Single
nucleotide
polymorphisms
associated
with
(p<5x10-6)
were
selected
as
instrumental
variables,
excluding
those
linkage
disequilibrium.
Inverse-variance
weighted
analysis
used
primary
method,
supplemented
by
MR
Egger,
median,
simple
mode
methods.
Sensitivity
analyses
included
heterogeneity,
horizontal
pleiotropy,
leave-one-out,
funnel
plot
assessments.
Multivariable
adjusted
for
smoking,
alcohol,
periodontitis
malnutrition
performed.
Results:
In
univariate
analysis,
increased
beta-nerve
growth
factor
(OR:
1.53,
95%
CI:
1.06–2.20),
decreased
macrophage
colony
stimulating
0.87,
0.78–0.98)
interleukin-18
0.80,
0.65–0.98)
causally
higher
risk.
multivariable
effects
of
1.63,
1.24–2.13)
,macrophage
factor(OR:0.87,
CI:0.75–1.00)and
0.82,
0.67–0.99)
remained
significant
after
adjusting
exposures.
No
reverse
causation
found.
Conclusions:
provides
evidence
along
risk,
independent
known
factors.
These
may
represent
etiologic
targets
prevention.
Molecular Cancer,
Journal Year:
2023,
Volume and Issue:
22(1)
Published: Nov. 27, 2023
Abstract
Immunotherapies
have
revolutionized
the
treatment
paradigms
of
various
types
cancers.
However,
most
these
immunomodulatory
strategies
focus
on
harnessing
adaptive
immunity,
mainly
by
inhibiting
immunosuppressive
signaling
with
immune
checkpoint
blockade,
or
enhancing
immunostimulatory
bispecific
T
cell
engager
and
chimeric
antigen
receptor
(CAR)-T
cell.
Although
agents
already
achieved
great
success,
only
a
tiny
percentage
patients
could
benefit
from
immunotherapies.
Actually,
immunotherapy
efficacy
is
determined
multiple
components
in
tumor
microenvironment
beyond
immunity.
Cells
innate
arm
system,
such
as
macrophages,
dendritic
cells,
myeloid-derived
suppressor
neutrophils,
natural
killer
unconventional
also
participate
cancer
evasion
surveillance.
Considering
that
cornerstone
antitumor
response,
utilizing
immunity
provides
potential
therapeutic
options
for
control.
Up
to
now,
exploiting
agonists
stimulator
interferon
genes,
CAR-macrophage
-natural
therapies,
metabolic
regulators,
novel
exhibited
potent
activities
preclinical
clinical
studies.
Here,
we
summarize
latest
insights
into
roles
cells
discuss
advances
arm-targeted
strategies.
Molecular Cancer,
Journal Year:
2024,
Volume and Issue:
23(1)
Published: June 1, 2024
Abstract
Significant
advancements
have
been
made
in
the
application
of
chimeric
antigen
receptor
(CAR)-T
treatment
for
blood
cancers
during
previous
ten
years.
However,
its
effectiveness
treating
solid
tumors
is
still
lacking,
necessitating
exploration
alternative
immunotherapies
that
can
overcome
significant
challenges
faced
by
current
CAR-T
cells.
CAR-based
immunotherapy
against
shows
promise
with
emergence
macrophages,
which
possess
robust
phagocytic
abilities,
antigen-presenting
functions,
and
ability
to
modify
tumor
microenvironment
stimulate
adaptive
responses.
This
paper
presents
a
thorough
examination
latest
progress
CAR-M
therapy,
covering
both
basic
scientific
studies
clinical
trials.
study
examines
primary
obstacles
hindering
realization
complete
potential
as
well
strategies
be
employed
these
hurdles.
With
revolutionary
technologies
like
situ
genetic
modification,
synthetic
biology
techniques,
biomaterial-supported
gene
transfer,
provide
wider
array
resources
manipulating
tumor-associated
we
suggest
combining
advanced
methods
will
result
creation
new
era
therapy
demonstrates
improved
efficacy,
safety,
availability.
Graphical
Immunological Reviews,
Journal Year:
2023,
Volume and Issue:
320(1), P. 166 - 198
Published: Aug. 7, 2023
Adoptive
T-cell
transfer
(ACT)
therapies,
including
of
tumor
infiltrating
lymphocytes
(TILs)
and
T
cells
gene-modified
to
express
either
a
cell
receptor
(TCR)
or
chimeric
antigen
(CAR),
have
demonstrated
clinical
efficacy
for
proportion
patients
cancer-types.
The
field
ACT
has
been
driven
forward
by
the
success
CD19-CAR
therapy
against
various
advanced
B-cell
malignancies,
curative
responses
some
leukemia
patients.
However,
relapse
remains
problematic,
in
particular
lymphoma.
Moreover,
variety
reasons,
relative
limited
non-hematological
solid
tumors.
Indeed,
addition
pre-infusion
challenges
lymphocyte
collection
manufacturing,
failure
can
be
attributed
several
biological
processes
post-transfer
including,
(i)
inefficient
trafficking,
infiltration,
expansion
retention,
(ii)
chronic
exposure
coupled
with
insufficient
costimulation
resulting
exhaustion,
(iii)
range
barriers
microenvironment
(TME)
mediated
both
suppressive
immune
infiltrate,
(iv)
heterogeneity
loss,
down-regulation
presentation
machinery,
(v)
gain
intrinsic
mechanisms
resistance
such
as
apoptosis,
(vi)
forms
toxicity
other
adverse
events
Affinity-optimized
TCRs
improve
function
innovative
CAR
designs
well
gene-modification
strategies
used
coengineer
specificity,
safety,
into
cells.
Coengineering
designed
not
only
directly
support
transferred
cells,
but
also
block
TME
harness
endogenous
innate
adaptive
immunity.
Here,
we
review
selection
remarkable
coengineering
strategies,
tools,
receptors,
gene-cargo,
that
developed
recent
years
augment
control
ACT,
more
which
are
advancing
clinic.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(11), P. 9235 - 9235
Published: May 25, 2023
Cancer
is
the
leading
cause
of
death
worldwide
despite
variety
treatments
that
are
currently
used.
This
due
to
an
innate
or
acquired
resistance
therapy
encourages
discovery
novel
therapeutic
strategies
overcome
resistance.
review
will
focus
on
role
purinergic
receptor
P2RX7
in
control
tumor
growth,
through
its
ability
modulate
antitumor
immunity
by
releasing
IL-18.
In
particular,
we
describe
how
ATP-induced
activities
(cationic
exchange,
large
pore
opening
and
NLRP3
inflammasome
activation)
immune
cell
functions.
Furthermore,
recapitulate
our
current
knowledge
production
IL-18
downstream
activation
controls
fate
growth.
Finally,
potential
targeting
P2RX7/IL-18
pathway
combination
with
classical
immunotherapies
fight
cancer
discussed.
EMBO Molecular Medicine,
Journal Year:
2023,
Volume and Issue:
15(11)
Published: Oct. 2, 2023
Abstract
NK‐cell
reactivity
against
cancer
is
conceivably
suppressed
in
the
tumor
microenvironment
by
interaction
of
inhibitory
receptor
NKG2A
with
non‐classical
MHC‐I
molecules
HLA‐E
humans
or
Qa‐1
b
mice.
We
found
that
intratumoral
delivery
NK
cells
attains
significant
therapeutic
effects
only
if
co‐injected
anti‐NKG2A
and
anti‐Qa‐1
blocking
monoclonal
antibodies
solid
mouse
models.
Such
activity
was
contingent
on
endogenous
CD8
T
type‐1
conventional
dendritic
(cDC1).
Moreover,
anti‐tumor
were
enhanced
upon
combination
systemic
anti‐PD‐1
mAb
treatment
achieved
partial
abscopal
efficacy
distant
non‐injected
tumors.
In
xenografted
mice
bearing
HLA‐E‐expressing
human
cells,
co‐injection
activated
allogeneic
clinical‐grade
(monalizumab)
synergistically
effects.
conclusion,
these
studies
provide
evidence
for
clinical
potential
cell‐based
immunotherapies
exert
their
as
a
result
eliciting
T‐cell
responses.
Cell Communication and Signaling,
Journal Year:
2023,
Volume and Issue:
21(1)
Published: Dec. 4, 2023
Abstract
T
cell-based
adoptive
cell
therapy
(ACT)
has
exhibited
excellent
antitumoral
efficacy
exemplified
by
the
clinical
breakthrough
of
chimeric
antigen
receptor
(CAR-T)
in
hematologic
malignancies.
It
relies
on
pool
functional
cells
to
retain
developmental
potential
serially
kill
targeted
cells.
However,
failure
continuous
supply
and
persistence
been
recognized
as
a
critical
barrier
sustainable
responses.
Conferring
stemness
infused
cells,
yielding
stem
cell-like
memory
(T
SCM
)
characterized
constant
self-renewal
multilineage
differentiation
similar
pluripotent
is
indeed
necessary
promising
for
enhancing
function
sustaining
antitumor
immunity.
Therefore,
it
crucial
identify
induction
regulators
acquire
more
resource
during
production
after
infusion
improve
efficacy.
Recently,
four
common
cytokine
γ
chain
(γc)
family
cytokines,
encompassing
interleukin-2
(IL-2),
IL-7,
IL-15,
IL-21,
have
widely
used
development
long-lived
adoptively
transferred
vitro.
challenges,
including
their
non-specific
toxicities
off-target
effects,
led
substantial
efforts
engineered
versions
unleash
full
maintenance
ACT.
In
this
review,
we
summarize
roles
γc
cytokines
orchestration
stemness,
introduce
that
modulate
formation
demonstrate
various
combinations.
Current Issues in Molecular Biology,
Journal Year:
2024,
Volume and Issue:
46(10), P. 11548 - 11579
Published: Oct. 16, 2024
Interleukin-12
(IL-12)
is
considered
to
be
a
promising
cytokine
for
enhancing
an
antitumor
immune
response;
however,
recombinant
IL-12
has
shown
significant
toxicity
and
limited
efficacy
in
early
clinical
trials.
Recently,
many
strategies
delivering
tumor
tissues
have
been
developed,
such
as
modifying
IL-12,
utilizing
viral
vectors,
non-viral
cellular
vectors.
Previous
studies
found
that
the
fusion
of
with
extracellular
matrix
proteins,
collagen,
factors
way
enhance
its
therapeutic
potential.
In
addition,
demonstrated
vectors
are
good
platform,
variety
viruses
oncolytic
viruses,
adenoviruses,
poxviruses
used
deliver
IL-12—with
testing
previously
conducted
various
cancer
models.
The
local
expression
tumors
based
on
delivery
avoids
systemic
while
inducing
effective
immunity
acting
synergistically
other
therapies
without
compromising
safety.
lipid
nanoparticles
currently
most
mature
drug
system.
Moreover,
cells
also
carriers
because
they
can
effectively
substances
tumors.
this
article,
we
will
systematically
discuss
anti-tumor
effects
own
or
combination
different
strategies.
