Journal for ImmunoTherapy of Cancer,
Год журнала:
2024,
Номер
12(12), С. e009910 - e009910
Опубликована: Дек. 1, 2024
Background
Chimeric
antigen
receptor
(CAR)
T
cells
have
demonstrated
remarkable
breakthroughs
in
treating
hematologic
malignancies,
yet
their
efficacy
solid
tumors
is
limited
by
the
immunosuppressive
microenvironment.
Sympathetic
nerves
significantly
contribute
to
this
milieu
tumors.
However,
impact
of
tumor
sympathetic
denervation
on
enhancing
CAR
T-cell
antitumor
remains
unclear.
Methods
We
screened
for
gene
sets
various
types
cancers
and
investigated
association
with
immunosuppression
renal
clear
cell
carcinoma.
Using
antibodies
block
nerve
growth
factor
(NGF)
pathway,
we
explored
distribution
tissues
progression.
Additionally,
engineered
secrete
NGF
single
chain
fragment
variable
(scFv)
achieve
immunosympathectomy
assessed
efficacy.
Bulk
RNA
sequencing
single-cell
analyses
were
conducted
evaluate
changes
immune
phenotypes
within
Results
Blocking
pathway
effectively
reduced
delayed
scFv
achieved
a
similar
exhibited
enhanced
suppression.
revealed
that
augmented
effect
was
primarily
due
inhibition
terminal
exhaustion
phenotype
tumor-infiltrating
CD8
prevention
macrophage
polarization
from
M1
M2.
This
approach
maintained
stronger
state
at
site.
splenic
also
more
potent
effector
following
infusion
scFv-secreting
cells.
Conclusions
Our
results
suggest
novel
weaken
microenvironment
synergistically
enhance
against
European Journal of Immunology,
Год журнала:
2024,
Номер
54(12)
Опубликована: Сен. 16, 2024
Lipid
nanoparticles
(LNPs)
have
emerged
as
the
preeminent
nonviral
drug
delivery
vehicles
for
nucleic
acid
therapeutics,
exemplified
by
their
usage
in
mRNA
COVID-19
vaccines.
As
a
safe
and
highly
modular
platform,
LNPs
are
attractive
wide
range
of
applications.
In
addition
to
vaccines,
being
utilized
platforms
other
immunoengineering
efforts,
especially
cancer
immunotherapies
modulating
immune
cells
functionality
via
delivery.
this
review,
we
focus
on
methods
applications
LNP-based
immunotherapy
five
cell
types:
T
cells,
NK
macrophages,
stem
dendritic
cells.
Each
these
types
has
wide-reaching
but
comes
with
unique
challenges
barriers.
By
combining
knowledge
immunology
nanotechnology,
can
be
developed
improved
targeting
transfection,
ultimately
working
toward
novel
clinical
therapeutics.
Cancer Drug Resistance,
Год журнала:
2023,
Номер
6(4), С. 748 - 67
Опубликована: Окт. 23, 2023
Tumors
survive
by
creating
a
tumor
microenvironment
(TME)
that
suppresses
antitumor
immunity.
The
TME
the
immune
system
limiting
antigen
presentation,
inhibiting
lymphocyte
and
natural
killer
(NK)
cell
activation,
facilitating
T
exhaustion.
Checkpoint
inhibitors
like
anti-PD-1
anti-CTLA
are
immunostimulatory
antibodies,
their
blockade
extends
survival
of
some
but
not
all
cancer
patients.
Extracellular
adenosine
triphosphate
(ATP)
is
abundant
in
inflamed
tumors,
its
metabolite,
(ADO),
driver
immunosuppression
mediated
A2A
receptors
(A2AR)
A2B
(A2BR)
found
on
tumor-associated
lymphoid
myeloid
cells.
This
review
will
focus
as
key
checkpoint
inhibitor-like
immunosuppressive
player
how
reducing
production
or
blocking
A2AR
A2BR
enhances
Cells,
Год журнала:
2023,
Номер
12(21), С. 2532 - 2532
Опубликована: Окт. 27, 2023
Many
cytokines
control
tumor
development
by
directly
lowering
cancer
cell
proliferation
and
inducing
apoptotic
death,
or
indirectly
activating
the
antitumoral
activity
of
specific
immune
cells
such
as
NK
CD8+
T-lymphocytes
[...]
According
to
the
CSC
hypothesis,
cancer
stem
cells
are
pivotal
in
initiating,
developing,
and
causing
recurrence.
Since
identification
of
CSCs
leukemia,
breast
cancer,
glioblastoma,
colorectal
1990s,
researchers
have
actively
investigated
origin
biology
CSCs.
However,
hypothesis
role
these
tumor
development
model
is
still
debate.
These
exhibit
distinct
surface
markers,
capable
self-renewal,
demonstrate
unrestricted
proliferation,
display
metabolic
adaptation.
phenotypic
plasticity
capacity
EMT
strictly
connected
stemness
state.
show
high
resistance
chemotherapy,
radiotherapy,
immunotherapy.
The
significantly
influenced
by
microenvironment
factors,
such
as
hypoxia.
Targeting
genetic
epigenetic
changes
cells,
together
with
interactions
microenvironment,
presents
promising
avenues
for
therapeutic
strategies.
See
also
Graphical
abstract(Fig.
1).
Journal for ImmunoTherapy of Cancer,
Год журнала:
2024,
Номер
12(12), С. e009910 - e009910
Опубликована: Дек. 1, 2024
Background
Chimeric
antigen
receptor
(CAR)
T
cells
have
demonstrated
remarkable
breakthroughs
in
treating
hematologic
malignancies,
yet
their
efficacy
solid
tumors
is
limited
by
the
immunosuppressive
microenvironment.
Sympathetic
nerves
significantly
contribute
to
this
milieu
tumors.
However,
impact
of
tumor
sympathetic
denervation
on
enhancing
CAR
T-cell
antitumor
remains
unclear.
Methods
We
screened
for
gene
sets
various
types
cancers
and
investigated
association
with
immunosuppression
renal
clear
cell
carcinoma.
Using
antibodies
block
nerve
growth
factor
(NGF)
pathway,
we
explored
distribution
tissues
progression.
Additionally,
engineered
secrete
NGF
single
chain
fragment
variable
(scFv)
achieve
immunosympathectomy
assessed
efficacy.
Bulk
RNA
sequencing
single-cell
analyses
were
conducted
evaluate
changes
immune
phenotypes
within
Results
Blocking
pathway
effectively
reduced
delayed
scFv
achieved
a
similar
exhibited
enhanced
suppression.
revealed
that
augmented
effect
was
primarily
due
inhibition
terminal
exhaustion
phenotype
tumor-infiltrating
CD8
prevention
macrophage
polarization
from
M1
M2.
This
approach
maintained
stronger
state
at
site.
splenic
also
more
potent
effector
following
infusion
scFv-secreting
cells.
Conclusions
Our
results
suggest
novel
weaken
microenvironment
synergistically
enhance
against
