Abstract
Cancer
immunotherapy
is
increasingly
used
in
clinical
practice,
but
its
success
rate
reduced
by
tumor
escape
from
the
immune
system.
This
may
be
due
to
genetic
instability
of
cells,
which
allows
them
adapt
response
and
leads
intratumoral
heterogeneity.
The
study
investigated
spatial
heterogeneity
microenvironment
possible
drivers
a
mouse
model
tumors
induced
human
papillomaviruses
(HPV)
following
immunotherapy.
Gene
expression
was
determined
RNA
sequencing
mutations
whole
exome
sequencing.
A
comparison
different
areas
revealed
cell
infiltration,
gene
expression,
mutation
composition.
While
mean
numbers
with
every
impact
on
or
protein
function
were
comparable
treated
control
tumors,
high
moderate
increased
after
genes
mutated
significantly
enriched
associated
ECM
metabolism,
degradation,
interactions,
HPV
infection
carcinogenesis,
processes
such
as
antigen
processing
presentation,
Toll‐like
receptor
signaling,
cytokine
production.
analysis
DNA
damage
repair
factors
that
upregulated
Apobec1
Apobec3
downregulated
related
homologous
recombination
translesion
synthesis.
In
conclusion,
this
describes
heterogeneity,
could
lead
escape,
suggests
potential
mechanisms
involved.
Despite
the
success
of
immunotherapy,
overcoming
immunoresistance
in
cancer
remains
challenging.
We
identified
a
unique
niche
tumor-associated
macrophages
(TAMs),
coexpressing
T
cell
immunoglobulin
and
mucin
domain–containing
3
(TIM3)
V-domain
suppressor
activation
(VISTA),
that
dominated
human
mouse
tumors
resistant
to
most
currently
used
immunotherapies.
TIM3
+
VISTA
TAMs
were
sustained
by
IL-4–enriching
with
low
(neo)antigenic
cell–depleted
features.
showed
an
anti-inflammatory
protumorigenic
phenotype
coupled
inability
sense
type
I
interferon
(IFN).
This
was
established
cells
succumbing
immunogenic
death
(ICD).
Dying
not
only
triggered
autocrine
IFNs
but
also
exposed
HMGB1/VISTA
engaged
TIM3/VISTA
on
suppress
paracrine
IFN-responses.
Accordingly,
blockade
synergized
paclitaxel,
ICD-inducing
chemotherapy,
repolarize
proinflammatory
killed
via
tumor
necrosis
factor–related
apoptosis-inducing
ligand
(TRAIL)
signaling.
propose
targeting
overcome
immunoresistant
tumors.
Abstract
Immunotherapy
has
recently
emerged
as
a
promising
therapeutic
modality
for
the
treatment
of
various
diseases
such
cancer,
inflammation,
autoimmune
diseases,
and
infectious
diseases.
Despite
its
potential,
immunotherapy
faces
challenges
related
to
delivery
efficiency
off‐target
toxicity
immunotherapeutic
drugs.
Nano
drug
systems
offer
improvements
in
biodistribution
release
kinetics
but
still
suffer
from
shortcomings
high
immunogenicity,
poor
penetration
across
biological
barriers,
insufficient
tissue
permeability.
Targeted
drugs
using
living
cells
become
an
emerging
strategy
that
can
take
advantage
inherent
characteristics
deal
with
defects
nano
systems.
Furthermore,
themselves
be
genetically
engineered
into
cellular
enhanced
immunotherapy.
This
review
provides
in‐depth
exploration
cell‐derived
carriers,
detailing
their
properties,
functions,
commonly
used
loading
strategies.
In
addition,
role
modified
synergistic
effects
are
also
introduced.
By
summarizing
main
advancements
limitations
field,
this
offers
insights
potential
cell‐based
address
existing
The
introduction
recent
developments
evaluation
ongoing
research
will
pave
way
optimization
widespread
adoption
nano/genetically
Abstract
Tissue‐resident
memory
T
(T
RM
)
cells
are
crucial
components
of
the
immune
system
that
provide
rapid,
localized
responses
to
recurrent
pathogens
at
mucosal
and
epithelial
barriers.
Unlike
circulating
cells,
located
within
peripheral
tissues,
they
play
vital
roles
in
antiviral,
antibacterial,
antitumor
immunity.
Their
unique
retention
activation
mechanisms,
including
interactions
with
local
expression
adhesion
molecules,
enable
their
persistence
immediate
functionality
diverse
tissues.
Recent
advances
have
revealed
important
chronic
inflammation,
autoimmunity,
cancer,
illuminating
both
protective
pathogenic
potential.
This
review
synthesizes
current
knowledge
on
cells’
molecular
signatures,
maintenance
pathways,
functional
dynamics
across
different
We
also
explore
other
such
as
B
macrophages,
dendritic
highlighting
complex
network
underpins
efficacy
surveillance
response.
Understanding
nuanced
regulation
is
essential
for
developing
targeted
therapeutic
strategies,
vaccines
immunotherapies,
enhance
while
mitigating
adverse
effects.
Insights
into
biology
hold
promise
innovative
treatments
infectious
diseases,
autoimmune
conditions.
Cancers,
Год журнала:
2025,
Номер
17(5), С. 879 - 879
Опубликована: Март 4, 2025
Malignant
glioma
is
a
highly
aggressive,
therapeutically
non-responsive,
and
deadly
disease
with
unique
tumor
microenvironment
(TME).
Of
the
14
currently
recognized
described
cancer
hallmarks,
five
are
especially
implicated
in
malignant
targetable
repurposed
drugs:
stem-like
cells,
general,
cells
particular
(GSCs),
vascularization
hypoxia,
metabolic
reprogramming,
tumor-promoting
inflammation
sustained
proliferative
signaling.
Each
hallmark
drives
development,
both
individually
through
interactions
other
which
TME
plays
critical
role.
To
combat
aggressive
spatio-temporal
heterogeneity
driven
by
interactions,
to
overcome
its
therapeutic
challenges,
combined
treatment
strategy
including
anticancer
therapies,
drugs
multimodal
immunotherapy
should
be
aim
for
future
approaches.
Dendritic
cells
(DCs)
are
critical
players
at
the
intersection
of
innate
and
adaptive
immunity,
making
them
ideal
candidates
for
anticancer
vaccine
development.
DC-based
immunotherapies
typically
involve
isolating
patient-derived
DCs,
pulsing
with
tumor-associated
antigens
(TAAs)
or
tumor-specific
(TSAs),
utilizing
maturation
cocktails
to
ensure
their
effective
activation.
These
matured
DCs
then
reinfused
elicit
T-cell
responses.
While
this
approach
has
demonstrated
ability
generate
potent
immune
responses,
its
clinical
efficacy
been
limited
due
immunosuppressive
tumor
microenvironment.
Recent
efforts
have
focused
on
enhancing
immunogenicity
vaccines,
particularly
through
combination
therapies
T
cell-targeting
immunotherapies.
This
Trial
Watch
summarizes
recent
advances
in
cancer
treatments,
including
development
new
preclinical
strategies,
discusses
future
potential
vaccines
evolving
landscape
immuno-oncology.
Although
dendritic
cell
(DC)-mediated
immunotherapies
are
effective
options
for
immunotherapy,
traditional
DC
vaccines
hampered
by
a
variety
of
drawbacks
such
as
insufficient
antigen
delivery,
weak
lymph
node
homing,
and
the
risk
living
transfusion.
To
address
above-mentioned
issues,
we
developed
personalized
DC-mimicking
nanovaccine
(HybridDC)
that
enhances
presentation
elicits
antitumor
immunity.
The
biomimetic
contains
membranes
derived
from
genetically
engineered
DCs,
several
cellular
components
simultaneously
anchored
onto
these
membranes,
including
CC-chemokine
receptor
7
(CCR7),
tumor-associated
antigenic
(TAA)
peptide/tumor-derived
exosome
(TEX),
relevant
costimulatory
molecules.
Compared
with
previous
vaccines,
HybridDC
vaccine
showed
an
increased
ability
to
target
lymphoid
tissues
reshape
immune
landscape
in
tumor
milieu.
demonstrated
significant
therapeutic
prophylactic
efficacy
poorly
immunogenic,
orthotopic
models
glioma.
Furthermore,
potentiates
checkpoint
blockade
(ICB)
therapy,
providing
potential
combination
strategy
maximize
ICB.
Specifically,
can
induce
long-term
protective
immunity
memory
T
cells.
Overall,
is
promising
platform
cancer
may
offer
combinational
modality
improve
current
immunotherapy.
Recently,
we
showed
that
an
autologous
DC-based
vaccine
induces
increase
in
immunosuppressive
PD-L1+
tumor-associated
macrophages
(TAM)
both
the
tumor
and
draining
lymph
nodes,
thereby
blunting
efficacy
of
therapeutic
immunization.
Only
combination
DC
with
anti-PD-L1
immune
checkpoint
inhibition,
but
not
use
antibodies
targeting
PD-1
alone,
was
able
to
set
off
CD8+
cytotoxic
T
lymphocyte
(CTL)-mediated
suppression
mice.
In
sum,
delineated
a
PD-L1
blockade-based
strategy
avoid
TAM-induced
cell
exhaustion
during
therapy.
