The Journal of Experimental Medicine,
Journal Year:
2022,
Volume and Issue:
219(5)
Published: April 11, 2022
The
resistance
of
pancreatic
ductal
adenocarcinoma
(PDAC)
to
immune
checkpoint
inhibitors
(ICIs)
is
attributed
the
immune-quiescent
and
-suppressive
tumor
microenvironment
(TME).
We
recently
found
that
CCR2
CCR5
were
induced
in
PDAC
following
treatment
with
anti-PD-1
antibody
(αPD-1);
thus,
we
examined
vaccine
or
radiation
therapy
(RT)
as
T
cell
priming
mechanisms
together
BMS-687681,
a
dual
antagonist
(CCR2/5i),
combination
αPD-1
new
strategies.
Using
mouse
models,
demonstrated
RT
followed
by
prolonged
CCR2/5i
conferred
better
antitumor
efficacy
than
other
treatments
tested.
+
enhanced
intratumoral
effector
memory
infiltration
but
suppressed
regulatory
cell,
M2-like
tumor-associated
macrophage,
myeloid-derived
suppressive
infiltration.
RNA
sequencing
showed
partially
inhibited
RT-induced
TLR2/4
RAGE
signaling,
leading
decreased
expression
immunosuppressive
cytokines
including
CCL2/CCL5,
increased
chemokines
such
CCL17/CCL22.
This
study
thus
supports
clinical
development
ICIs
for
treatment.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: July 29, 2022
Abstract
Radiotherapy
(RT)
is
delivered
for
purposes
of
local
control,
but
can
also
exert
systemic
effect
on
remote
and
non-irradiated
tumor
deposits,
which
called
abscopal
effect.
The
view
RT
as
a
simple
treatment
has
dramatically
changed
in
recent
years,
it
now
widely
accepted
that
provoke
immune
response
gives
strong
rationale
the
combination
immunotherapy
(iRT).
Nevertheless,
several
points
remain
to
be
addressed
such
interaction
system,
identification
best
schedules
with
(IO),
expansion
mechanism
amplify
iRT.
To
answer
these
crucial
questions,
we
roundly
summarize
underlying
showing
whole
landscape
clinical
trials
attempt
identify
In
consideration
rarity
effect,
propose
occurrence
induced
by
radiation
promoted
100%
molecular
genetic
level.
Furthermore,
“radscopal
effect”
refers
using
low-dose
reprogram
microenvironment
may
overcome
resistance
Taken
together,
could
regarded
trigger
antitumor
response,
help
IO
used
radical
added
into
current
standard
regimen
patients
metastatic
cancer.
Pharmaceutics,
Journal Year:
2020,
Volume and Issue:
12(12), P. 1186 - 1186
Published: Dec. 6, 2020
Most
cancer
biologists
still
rely
on
conventional
two-dimensional
(2D)
monolayer
culture
techniques
to
test
in
vitro
anti-tumor
drugs
prior
vivo
testing.
However,
the
vast
majority
of
promising
preclinical
have
no
or
weak
efficacy
real
patients
with
tumors,
thereby
delaying
discovery
successful
therapeutics.
This
is
because
2D
lacks
cell–cell
contacts
and
natural
tumor
microenvironment,
important
signaling
drug
response,
resulting
a
reduced
malignant
phenotype
compared
tumor.
In
this
sense,
three-dimensional
(3D)
cultures
cells
that
better
recapitulate
cell
environments
emerged
as
scientifically
accurate
low
cost
models
for
screening
testing
new
candidates
before
moving
expensive
time-consuming
animal
models.
Here,
we
provide
comprehensive
overview
3D
systems
highlight
strategies
spheroid
construction
evaluation
tools
targeted
therapies,
focusing
their
applicability
research.
Examples
therapeutic
nanomedicines
are
discussed.
Journal of Nanobiotechnology,
Journal Year:
2022,
Volume and Issue:
20(1)
Published: Feb. 22, 2022
Nanozyme
is
a
series
of
nanomaterials
with
enzyme-mimetic
activities
that
can
proceed
the
catalytic
reactions
natural
enzymes.
In
field
biomedicine,
nanozymes
are
capturing
tremendous
attention
due
to
their
high
stability
and
low
cost.
Enzyme-mimetic
be
regulated
by
multiple
factors,
such
as
chemical
state
metal
ion,
pH,
hydrogen
peroxide
(H2O2),
glutathione
(GSH)
level,
presenting
great
promise
for
biomedical
applications.
Over
past
decade,
multi-functional
have
been
developed
various
To
promote
understandings
development
novel
multifunctional
nanozymes,
we
herein
provide
comprehensive
review
applications
in
field.
Nanozymes
versatile
enzyme-like
properties
briefly
overviewed,
mechanism
application
discussed
future
research.
Finally,
underlying
challenges
prospects
frontier
this
review.
Frontiers in Immunology,
Journal Year:
2022,
Volume and Issue:
13
Published: March 30, 2022
The
demise
of
cells
in
various
ways
enables
the
body
to
clear
unwanted
cells.
Studies
over
years
revealed
distinctive
molecular
mechanisms
and
functional
consequences
several
key
cell
death
pathways.
Currently,
most
intensively
investigated
programmed
(PCD)
includes
apoptosis,
necroptosis,
pyroptosis,
ferroptosis,
PANoptosis,
autophagy,
which
has
been
discovered
play
crucial
roles
modulating
immunosuppressive
tumor
microenvironment
(TME)
determining
clinical
outcomes
cancer
therapeutic
approaches.
PCD
can
dual
roles,
either
pro-tumor
or
anti-tumor,
partly
depending
on
intracellular
contents
released
during
process.
also
regulates
enrichment
effector
regulatory
immune
cells,
thus
participating
fine-tuning
anti-tumor
immunity
TME.
In
this
review,
we
focused
primarily
discussed
messengers
regulating
their
intricate
crosstalk
with
response
TME,
explored
immunological
consequence
its
implications
future
therapy
developments.
Frontiers in Oncology,
Journal Year:
2020,
Volume and Issue:
10
Published: Feb. 20, 2020
Cancer
stem
cells
(CSC)
are
a
distinct
subpopulation
within
tumor.
They
able
to
self-renew
and
differentiate
possess
high
capability
repair
DNA
damage,
exhibit
low
levels
of
reactive
oxygen
species
(ROS),
proliferate
slowly.
These
features
render
CSC
resistant
various
therapies,
including
radiation
therapy
(RT).
Eradication
as
many
possible
is
requirement
for
an
effective
antineoplastic
treatment
therefore
utmost
importance
the
patient.
This
makes
prime
targets
any
therapeutic
approach.
Albeit
clinical
data
still
scarce,
experimental
first
trials
give
hope
that
CSC-based
has
potential
improve
treatment,
especially
tumors
known
be
resistant,
such
glioblastoma.
In
this
review,
we
will
discuss
in
context
RT,
describe
mechanisms
resistance,
examine
possibilities
biomarkers,
new
approaches.
Cells,
Journal Year:
2020,
Volume and Issue:
9(7), P. 1651 - 1651
Published: July 9, 2020
Radiotherapy
(RT)
is
a
modality
of
oncologic
treatment
that
can
be
used
to
treat
approximately
50%
all
cancer
patients
either
alone
or
in
combination
with
other
modalities
such
as
surgery,
chemotherapy,
immunotherapy,
and
therapeutic
targeting.
Despite
the
technological
advances
RT,
which
allow
more
precise
delivery
radiation
while
progressively
minimizing
impact
on
normal
tissues,
issues
like
radioresistance
tumor
recurrence
remain
important
challenges.
Tumor
heterogeneity
responsible
for
variation
response
different
subpopulations.
A
main
factor
related
presence
stem
cells
(CSC)
inside
tumors,
are
metastases,
relapses,
RT
failure,
poor
prognosis
patients.
The
plasticity
CSCs,
process
highly
dependent
epithelial–mesenchymal
transition
(EMT)
associated
cell
dedifferentiation,
complicates
identification
eradication
CSCs
it
might
involved
disease
relapse
progression
after
irradiation.
microenvironment
interactions
their
niches
also
play
an
role
RT.
This
review
provides
deep
insight
into
characteristics
mechanisms
both
primary
metastasis
radiation,
radiobiological
principles
CSC
Finally,
we
summarize
major
clinical
trials
development
CSC-based
therapies
combined
overcome
radioresistance.
better
understanding
potential
targets
radiosensitization
will
provide
safer
efficient
strategies,
turn
improve
live
expectancy
curability
Environment International,
Journal Year:
2020,
Volume and Issue:
149, P. 106212 - 106212
Published: Dec. 5, 2020
Ionizing
radiation
interacts
with
the
immune
system
in
many
ways
a
multiplicity
that
mirrors
complexity
of
itself:
namely
need
to
maintain
delicate
balance
between
different
compartments,
cells
and
soluble
factors
work
collectively
protect,
maintain,
restore
tissue
function
face
severe
challenges
including
damage.
The
cytotoxic
effects
high
dose
are
less
relevant
after
low
exposure,
where
subtle
quantitative
functional
predominate
may
go
unnoticed
until
late
exposure
or
second
challenge
reveals
exacerbates
effects.
For
example,
doses
permanently
alter
fitness
therefore
accelerate
senescence
pave
way
for
wide
spectrum
possible
pathophysiological
events,
early-onset
age-related
degenerative
disorders
cancer.
By
contrast,
so
called
therapy
displays
beneficial,
anti-inflammatory
pain
relieving
properties
chronic
inflammatory
diseases.
In
this
review,
epidemiological,
clinical
experimental
data
regarding
low-dose
on
homeostasis
integrity
will
be
discussed,
as
role
immune-mediated
mechanisms
systemic
manifestation
localized
exposures
such
reactions.
central
conclusion
is
ionizing
fundamentally
durably
reshapes
system.
Further,
importance
discovery
immunological
pathways
modifying
resilience
amongst
other
research
directions
field
implied.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2020,
Volume and Issue:
39(1)
Published: April 16, 2020
Tumor
microenvironment
(TME)
is
the
internal
environment
in
which
tumor
cells
survive,
consisting
of
cells,
fibroblasts,
endothelial
and
immune
as
well
non-cellular
components,
such
exosomes
cytokines.
Exosomes
are
tiny
extracellular
vesicles
(40-160nm)
containing
active
substances,
proteins,
lipids
nucleic
acids.
carry
biologically
miRNAs
to
shuttle
between
TME,
thereby
affecting
development.
Tumor-derived
exosomal
induce
matrix
reprogramming
creating
a
that
conducive
growth,
metastasis,
escape
chemotherapy
resistance.
In
this
review,
we
updated
role
process
TME
reshaping.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2021,
Volume and Issue:
40(1)
Published: June 21, 2021
Hypoxia
in
solid
tumors
is
an
important
predictor
of
treatment
resistance
and
poor
clinical
outcome.
The
significance
hypoxia
the
development
to
radiotherapy
has
been
recognized
for
decades
search
hypoxia-targeting,
radiosensitizing
agents
continues.
This
review
summarizes
main
hypoxia-related
processes
relevant
on
subcellular,
cellular
tissue
level
discusses
radiation
oncology,
especially
with
regard
current
shift
towards
hypofractionated
regimens.
Furthermore,
we
discuss
strategies
interfere
optimization,
highlight
novel
insights
into
molecular
pathways
involved
that
might
be
utilized
increase
efficacy
radiotherapy.
Cancers,
Journal Year:
2023,
Volume and Issue:
15(2), P. 376 - 376
Published: Jan. 6, 2023
Tumorigenesis
is
a
complex
and
dynamic
process
involving
cell-cell
cell-extracellular
matrix
(ECM)
interactions
that
allow
tumor
cell
growth,
drug
resistance
metastasis.
This
review
provides
an
updated
summary
of
the
role
played
by
microenvironment
(TME)
components
hypoxia
in
tumorigenesis,
highlight
various
ways
through
which
cells
reprogram
normal
into
phenotypes
are
pro-tumorigenic,
including
cancer
associated-
fibroblasts,
-macrophages
-endothelial
cells.
Tumor
secrete
numerous
factors
leading
to
transformation
previously
anti-tumorigenic
environment
pro-tumorigenic
environment.
Once
formed,
solid
tumors
continue
interact
with
stromal
cells,
local
infiltrating
macrophages,
mesenchymal
stem
endothelial
pericytes,
secreted
ECM
within
(TME).
The
TME
key
response
treatment
outcome.
Importantly,
can
initially
be
anti-tumorigenic,
but
over
time
promote
tumorigenesis
induce
therapy
resistance.
To
counter
hypoxia,
increased
angiogenesis
leads
formation
new
vascular
networks
order
actively
sustain
growth
via
supply
oxygen
nutrients,
whilst
removing
metabolic
waste.
Angiogenic
network
aid
metastatic
dissemination.
Successful
novel
development
require
identification
therapeutic
targeting
cancer-associated-
fibroblasts
(CAFs)
(CAMs),
blocking
ECM-receptor
interactions,
addition
reprogramming
immune
success.
Lastly,
this
highlights
potential
TME-
hypoxia-centered
therapies
under
investigation.