Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: July 22, 2024
Abstract
Cytokines
are
critical
in
regulating
immune
responses
and
cellular
behavior,
playing
dual
roles
both
normal
physiology
the
pathology
of
diseases
such
as
cancer.
These
molecules,
including
interleukins,
interferons,
tumor
necrosis
factors,
chemokines,
growth
factors
like
TGF-β,
VEGF,
EGF,
can
promote
or
inhibit
growth,
influence
microenvironment,
impact
efficacy
cancer
treatments.
Recent
advances
targeting
these
pathways
have
shown
promising
therapeutic
potential,
offering
new
strategies
to
modulate
system,
progression,
overcome
resistance
conventional
therapies.
In
this
review,
we
summarized
current
understanding
implications
cytokine
chemokine
signaling
By
exploring
molecules
biology
response,
highlighted
development
novel
agents
aimed
at
modulating
combat
The
review
elaborated
on
nature
cytokines
promoters
suppressors
tumorigenesis,
depending
context,
discussed
challenges
opportunities
presents
for
intervention.
We
also
examined
latest
advancements
targeted
therapies,
monoclonal
antibodies,
bispecific
receptor
inhibitors,
fusion
proteins,
engineered
variants,
their
metastasis,
microenvironment.
Additionally,
evaluated
potential
combining
therapies
with
other
treatment
modalities
improve
patient
outcomes.
Besides,
focused
ongoing
research
clinical
trials
that
pivotal
advancing
our
application
cytokine-
chemokine-targeted
patients.
Cancer Discovery,
Journal Year:
2024,
Volume and Issue:
14(7), P. 1206 - 1225
Published: April 2, 2024
Abstract
IL2
signals
pleiotropically
on
diverse
cell
types,
some
of
which
contribute
to
therapeutic
activity
against
tumors,
whereas
others
drive
undesired
activity,
such
as
immunosuppression
or
toxicity.
We
explored
the
theory
that
targeting
CD8+
T
cells,
are
key
antitumor
effectors,
could
enhance
its
index.
To
this
aim,
we
developed
AB248,
a
CD8
cis-targeted
demonstrates
over
500-fold
preference
for
cells
natural
killer
and
regulatory
(Tregs),
may
toxicity
immunosuppression,
respectively.
AB248
recapitulated
IL2’s
effects
in
vitro
induced
selective
expansion
CD8+T
primates.
In
mice,
an
surrogate
demonstrated
superior
enhanced
tolerability
compared
with
untargeted
IL2Rβγ
agonist.
Efficacy
was
associated
phenotypic
enhancement
tumor-infiltrating
including
emergence
“better
effector”
population.
These
data
support
potential
utility
clinical
settings.
Significance:
The
full
therapy
remains
be
unlocked.
demonstrate
can
decoupled
from
preclinical
models
by
limiting
signaling
supporting
development
cell–selective
treatment
cancer.
See
related
article
Kaptein
et
al.
p.
1226.
Journal of Clinical Investigation,
Journal Year:
2024,
Volume and Issue:
134(14)
Published: May 23, 2024
Intratumoral
regulatory
T
cells
(Tregs)
are
key
mediators
of
cancer
immunotherapy
resistance,
including
anti-PD-(L)1
immune
checkpoint
blockade
(ICB).
The
mechanisms
driving
Treg
infiltration
into
the
tumor
microenvironment
(TME)
and
consequence
on
CD8+
cell
exhaustion
remains
elusive.
Herein,
we
report
that
heat
shock
protein
gp96
(GRP94)
is
indispensable
for
infiltration,
primarily
through
gp96's
roles
in
chaperoning
integrins.
Among
various
gp96-dependent
integrins,
found
only
LFA-1
(αL
integrin)
but
not
αV,
CD103
(αE)
or
β7
integrin
was
required
homing.
Loss
TME
by
genetically
deleting
gp96/LFA-1
potently
induces
rejection
multiple
ICB-resistant
murine
models
a
cell-dependent
manner
without
loss
self-tolerance.
Moreover,
deletion
impeded
activation
suppressing
IL-2/STAT5
signaling,
which
also
contributes
to
regression.
By
competing
intratumoral
IL-2,
Tregs
prevent
tumor-infiltrating
lymphocytes
(TILs),
drive
TOX
induction
induce
bona
fide
exhaustion.
contrast,
ablation
leads
striking
induction,
demonstrating
clear
uncoupling
two
processes.
Our
study
reveals
axis
plays
fundamental
role
biology
suggests
Treg-specific
targeting
represents
valuable
strategy
inflicting
autoinflammatory
conditions.
Cancer Biology and Medicine,
Journal Year:
2024,
Volume and Issue:
unknown, P. 1 - 14
Published: May 31, 2024
In
exploring
persistent
infections
and
malignancies,
a
distinctive
subgroup
of
CD8+
T
cells,
progenitor
exhausted
(Tpex)
has
been
identified.
These
Tpex
cells
are
notable
for
their
remarkable
self-renewal
rapid
proliferation
abilities.
Recent
strides
in
immunotherapy
have
demonstrated
that
expand
differentiate
into
responsive
thus
underscoring
critical
role
the
immunotherapeutic
retort.
Clinical
examinations
further
clarified
robust
positive
correlation
between
proportional
abundance
enhanced
clinical
prognosis.
found
noteworthy
applications
formulation
inventive
approaches
against
tumors.
This
review
describes
functions
tumor
milieu,
particularly
potential
utility
immunotherapy.
Precisely
directing
may
be
essential
to
achieving
successful
outcomes
Advanced Materials,
Journal Year:
2024,
Volume and Issue:
36(44)
Published: Sept. 12, 2024
Abstract
Improving
clinical
immunotherapy
for
glioblastoma
(GBM)
relies
on
addressing
the
immunosuppressive
tumor
microenvironment
(TME).
Enhancing
CD8
+
T
cell
infiltration
and
preventing
its
exhaustion
holds
promise
effective
GBM
immunotherapy.
Here,
a
low‐intensity
focused
ultrasound
(LIFU)‐guided
sequential
delivery
strategy
is
developed
to
enhance
cells
activity
in
region.
The
of
CXC
chemokine
ligand
10
(CXCL10)
recruit
interleukin‐2
(IL‐2)
reduce
their
termed
an
“open‐source
throttling”
strategy.
Consequently,
up
3.39‐fold
are
observed
with
LIFU‐guided
CXCL10,
IL‐2,
anti‐programmed
death
1
(aPD‐L1),
compared
free
aPD‐L1
group.
immune
checkpoint
inhibitors
(ICIs)
therapeutic
efficacy
substantially
enhanced
by
reversed
TME
due
expansion
cells,
resulting
elimination
tumor,
prolonged
survival
time,
long‐term
memory
establishment
orthotopic
mice.
Overall,
cytokine
ICIs
offers
which
may
present
promising
brain‐tumor
International Journal of General Medicine,
Journal Year:
2025,
Volume and Issue:
Volume 18, P. 529 - 565
Published: Feb. 1, 2025
Abstract:
Allergic
rhinitis
(AR)
is
a
prevalent
allergic
disease
that
imposes
significant
economic
burdens
and
life
pressures
on
individuals,
families,
society,
particularly
in
the
context
of
accelerating
globalization
increasing
pathogenic
factors.
Current
clinical
therapies
for
AR
include
antihistamines,
glucocorticoids
administered
via
various
routes,
leukotriene
receptor
antagonists,
immunotherapy,
several
decongestants.
These
treatments
have
demonstrated
efficacy
alleviating
symptoms
pathological
states.
However,
with
growing
awareness
rising
expectations
improvements
quality
life,
these
become
associated
higher
incidence
side
effects
an
elevated
risk
drug
resistance.
Furthermore,
development
intricately
dysregulation
immune
system,
yet
underlying
pathogenetic
mechanisms
remain
incompletely
understood.
In
contrast,
widely
available
natural
plant
molecules
offer
multiple
targeting
pathways
uniquely
modify
typical
pathophysiology
through
immunomodulatory
processes.
This
review
presents
comprehensive
analysis
both
vivo
vitro
studies
modulate
immunity
treating
AR.
Additionally,
we
examine
their
specific
action
animal
models
to
provide
new
insights
developing
safe
effective
targeted
while
guiding
experimental
applications
against
Keywords:
molecules,
rhinitis,
immunomodulation,
therapeutic
mechanism,
research
progress
