Cancers,
Journal Year:
2024,
Volume and Issue:
16(17), P. 3069 - 3069
Published: Sept. 3, 2024
Mutation
in
p53
is
the
most
frequent
event
cancer
development
and
a
leading
cause
of
therapy
resistance
due
to
evasion
apoptosis
cascade.
Beyond
chemotherapies
radiation
therapies,
growing
evidence
indicates
that
p53-mutant
tumors
are
resistant
broad
range
immune-based
such
as
immune
checkpoint
inhibitors,
chimeric
antigen
receptor
(CAR)
T,
hematopoietic
stem
cell
transplantation
(HSCT).
This
highlights
role
mutations
driving
tumor
cells.
In
this
review,
we
first
summarize
recent
studies
revealing
mechanisms
by
which
evade
surveillance
from
T
cells,
natural
killer
(NK)
macrophages.
We
then
review
how
these
mutant
cells
reshape
microenvironment
(TME),
modulating
bystander
macrophages,
neutrophils,
regulatory
(Treg)
foster
immunosuppression.
Additionally,
clinical
observations
indicative
associated
with
loss
or
mutations.
Finally,
discuss
therapeutic
strategies
enhance
response
wild-type
(WT)
tumors.
npj Precision Oncology,
Journal Year:
2024,
Volume and Issue:
8(1)
Published: Feb. 10, 2024
Abstract
Tumor
drug
resistance
emerges
from
the
interaction
of
two
critical
factors:
tumor
cellular
heterogeneity
and
immunosuppressive
nature
microenvironment
(TME).
Tumor-associated
macrophages
(TAMs)
constitute
essential
components
TME.
M2-like
TAMs
are
in
facilitating
metastasis
as
well
augmenting
tumors.
This
review
encapsulates
mechanisms
that
use
to
promote
resistance.
We
also
describe
emerging
therapeutic
strategies
currently
targeting
combination
with
other
antitumor
drugs,
some
still
undergoing
clinical
trial
evaluation.
Furthermore,
we
summarize
analyze
various
existing
approaches
for
developing
novel
drugs
target
overcome
resistance,
highlighting
how
can
effectively
stop
growth,
metastasis,
Molecular Cancer,
Journal Year:
2023,
Volume and Issue:
22(1)
Published: Feb. 10, 2023
Abstract
In
recent
years,
breakthroughs
have
been
made
in
tumor
immunotherapy.
However,
immunotherapy,
particularly
anti-PD-1/PD-L1
immune
checkpoint
inhibitors,
is
effective
only
a
small
percentage
of
patients
solid
cancer.
How
to
improve
the
efficiency
cancer
immunotherapy
an
urgent
problem
be
solved.
As
we
all
know,
state
microenvironment
(TME)
essential
factor
affecting
effectiveness
and
cancer-associated
fibroblasts
(CAFs)
TME
attracted
much
attention
years.
one
main
components
TME,
CAFs
interact
with
cells
by
secreting
cytokines
vesicles,
participating
ECM
remodeling,
finally
response
process.
With
in-depth
study
heterogeneity,
new
strategies
are
provided
for
finding
targets
combination
predicting
efficacy.
this
review,
focus
on
role
microenvironment,
then
further
elaborate
potential
mechanisms
pathways
influencing
addition,
summarize
clinical
application
value
CAFs-related
markers
cancers.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Nov. 16, 2023
Cancer
progression
is
primarily
caused
by
interactions
between
transformed
cells
and
the
components
of
tumor
microenvironment
(TME).
TAMs
(tumor-associated
macrophages)
make
up
majority
invading
immune
components,
which
are
further
categorized
as
anti-tumor
M1
pro-tumor
M2
subtypes.
While
known
to
have
anti-cancer
properties,
recognized
extend
a
protective
role
tumor.
As
result,
manipulates
TME
in
such
way
that
it
induces
macrophage
infiltration
switching
bias
secure
its
survival.
This
M2-TAM
promotes
cancer
cell
proliferation,
neoangiogenesis,
lymphangiogenesis,
epithelial-to-mesenchymal
transition,
matrix
remodeling
for
metastatic
support,
manipulation
an
immunosuppressive
state.
additionally
promote
emergence
stem
(CSCs),
their
ability
originate,
metastasize,
relapse
into
tumors.
CSCs
also
help
revealing
escape
survival
strategies
during
initiation
phases.
review
describes
reasons
immunotherapy
failure
and,
thereby,
devises
better
impair
tumor-TAM
crosstalk.
study
will
shed
light
on
understudied
TAM-mediated
address
much-needed
holistic
approach
therapy,
encompasses
targeting
cells,
CSCs,
all
at
same
time.
ACS Nano,
Journal Year:
2023,
Volume and Issue:
17(2), P. 1583 - 1596
Published: Jan. 3, 2023
The
immunotherapeutic
effect
elicited
by
photodynamic
therapy
(PDT)
is
attenuated
tumor
defense
mechanisms
associated
with
glutamine
metabolism,
including
the
metabolic
regulation
of
redox
homeostasis
and
limitation
immunosuppressive
microenvironment
(ITM).
Herein,
a
carrier-free
nanobooster
C9SN
dual
synergistic
effects
was
constructed
self-assembly
glutaminase
(GLS)
inhibitor
compound
968
(C968)
photosensitizer
Chlorin
e6.
C968-mediated
GSH
deprivation
through
inhibiting
metabolism
prevented
PDT-generated
reactive
oxygen
species
from
being
annihilated
GSH,
amplifying
intracellular
oxidative
stress,
which
caused
severe
cell
death
also
enhanced
immunogenic
(ICD)
effect.
In
addition,
genome-wide
analysis
carried
out
using
RNA-sequencing
to
evaluate
changes
in
transcriptome
induced
stress.
Thereafter,
neoantigens
generated
ICD
promoted
maturation
dendritic
cells,
thereby
recruiting
activating
cytotoxic
T
lymphocytes
(CTLs).
Meanwhile,
remodeled
ITM
blocking
polarize
M2-type
tumor-associated
macrophages
(TAMs)
into
M1-type
TAMs,
further
recruited
activated
CTLs.
Ultimately,
this
suppressed
primary
distant
tumors.
This
"kill
two
birds
one
stone"
strategy
would
shed
light
on
enhancing
immunogenicity
alleviating
immunosuppression
improve
PDT.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
35(35)
Published: June 29, 2023
Immunomodulation
of
tumor-associated
macrophages
(TAMs)
into
tumor-inhibiting
M1-like
phenotype
is
a
promising
but
challenging
strategy.
Cleverly,
tumor
cells
overexpress
CD47,
"don't
eat
me"
signal
that
ligates
with
the
regulatory
protein
alpha
(SIRPα)
on
to
escape
phagocytosis.
Thus,
effective
re-education
TAMs
"eat
type
and
blocking
CD47-SIRPα
signaling
play
pivotal
roles
in
immunotherapy.
Herein,
it
reported
hybrid
nanovesicles
(hEL-RS17)
derived
from
extracellular
vesicles
M1
decorated
RS17
peptide,
an
antitumor
peptide
specifically
binds
CD47
blocks
signaling,
can
actively
target
remodel
TAM
phenotypes.
Consequently,
more
infiltrate
tissue
phagocytize
due
blockade.
By
further
co-encapsulating
chemotherapeutic
agent
shikonin,
photosensitizer
IR820,
immunomodulator
polymetformin
hEL-RS17,
enhanced
effect
obtained
combinational
treatment
modality
close
synergy
among
each
component.
Upon
laser
irradiation,
designed
SPI@hEL-RS17
nanoparticles
exert
potent
efficacy
against
both
4T1
breast
B16F10
melanoma
models,
which
not
only
suppresses
primary
growth
also
inhibits
lung
metastasis
prevents
recurrence,
exhibiting
great
potential
boosting
blockade-based
Journal of Cancer Research and Clinical Oncology,
Journal Year:
2024,
Volume and Issue:
150(5)
Published: May 7, 2024
Abstract
Background
Tumor
growth
is
closely
linked
to
the
activities
of
various
cells
in
tumor
microenvironment
(TME),
particularly
immune
cells.
During
progression,
circulating
monocytes
and
macrophages
are
recruited,
altering
TME
accelerating
growth.
These
adjust
their
functions
response
signals
from
stromal
Tumor-associated
(TAMs),
similar
M2
macrophages,
key
regulators
TME.
Methods
We
review
origins,
characteristics,
TAMs
within
This
analysis
includes
mechanisms
through
which
facilitate
evasion
promote
metastasis.
Additionally,
we
explore
potential
therapeutic
strategies
that
target
TAMs.
Results
instrumental
mediating
malignant
behaviors.
They
release
cytokines
inhibit
effector
attract
additional
immunosuppressive
primarily
T
cells,
inducing
exhaustion
directly,
influencing
activity
indirectly
cellular
interactions,
or
suppressing
checkpoints.
directly
involved
proliferation,
angiogenesis,
invasion,
Summary
Developing
innovative
tumor-targeted
therapies
immunotherapeutic
currently
a
promising
focus
oncology.
Given
pivotal
role
evasion,
several
approaches
have
been
devised
them.
include
leveraging
epigenetics,
metabolic
reprogramming,
engineering
repolarize
TAMs,
inhibiting
recruitment
activity,
using
as
drug
delivery
vehicles.
Although
some
these
remain
distant
clinical
application,
believe
future
targeting
will
offer
significant
benefits
cancer
patients.
Advanced Materials,
Journal Year:
2024,
Volume and Issue:
36(35)
Published: June 27, 2024
Cuproptosis
is
a
novel
copper-dependent
programmed
cell
death.
The
efficacy
of
cuproptosis
highly
dependent
on
intracellular
copper
accumulation
and
counteracted
by
high
level
glutathione
(GSH)
in
tumor
cells.
Here,
this
work
develops
self-amplified
nanoparticles
(Cel-Cu
NP)
using
celastrol
(Cel),
natural
product
isolated
from
medical
plant.
In
Cel-Cu
NP,
Cel
serves
as
versatile
ionophore,
exhibiting
an
ideal
coordination
capacity
toward
ions
without
compromising
the
induction.
Notably,
can
simultaneously
scavenge
GSH
content
to
amplify
cuproptosis.
Moreover,
further
activates
immunogenic
death
(ICD)
elicit
robust
immune
response.
Combining
with
checkpoint
blockade,
NP
effectively
eradicates
metastatic
tumors
mouse
lung
metastasis
model.
This
study
provides
efficient
nanomedicine
inducing
for
immunotherapy.
Journal of Nanobiotechnology,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: Jan. 28, 2024
Malignancy
is
a
major
public
health
problem
and
among
the
leading
lethal
diseases
worldwide.
Although
current
tumor
treatment
methods
have
therapeutic
effect
to
certain
extent,
they
still
some
shortcomings
such
as
poor
water
solubility,
short
half-life,
local
systemic
toxicity.
Therefore,
how
deliver
agent
so
realize
safe
effective
anti-tumor
therapy
become
urgently
be
solved
in
this
field.
As
medium
of
information
exchange
material
transport
between
cells,
exosomes
are
considered
promising
drug
delivery
carrier
due
their
nano-size,
good
biocompatibility,
natural
targeting,
easy
modification.
In
review,
we
summarize
recent
advances
isolation,
identification,
loading,
modification
carriers
for
alongside
application
therapy.
Basic
knowledge
exosomes,
biogenesis,
sources,
characterization
methods,
also
introduced
herein.
addition,
challenges
related
use
vehicles
discussed,
along
with
future
trends.
This
review
provides
scientific
basis
exosome
systems
oncological