Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: April 9, 2025
Gemcitabine
(GEM),
a
nucleoside
analog
chemotherapy
agent,
has
been
widely
used
in
the
treatment
of
various
cancers.
In
recent
years,
there
growing
interest
understanding
immunomodulatory
or
immunosuppressive
effects
GEM.
The
roles
GEM
could
influence
anti-tumor
immune
responses
via
several
mechanisms,
such
as
modulation
antigen
presentation,
cytokine
production,
and
cell
population.
Furthermore,
is
evidence
that
enhances
therapeutic
efficacy
immunotherapies,
including
oncolytic
viruses,
checkpoint
inhibitors,
CAR
T-cells,
vaccines.
On
other
hand,
accumulating
also
proposed
may
act
an
agent
within
tumor
microenvironment,
resulting
evasion
cells
growth.
These
paradoxical
modifying
highlight
complexity
interaction
with
microenvironment.
This
review
aims
to
provide
overview
microenvironment
how
affects
cancer
immunotherapy.
Annals of Laboratory Medicine,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 8, 2025
Joo
Dong
Park,
M.S.,
Ha
Eun
Shin,
Ph.D.,
Yeon
Su
An,
B.S.,
Hye
Jung
Jang,
Juwon
Se-Na
Kim,
Chun
Gwon
and
Wooram
Ph.D..
Ann
Lab
Med
-0001;0:.
https://doi.org/10.3343/alm.2024.0380
Experimental Hematology and Oncology,
Journal Year:
2024,
Volume and Issue:
13(1)
Published: Aug. 5, 2024
Abstract
Chimeric
antigen
receptor
macrophage
(CAR-MΦ)
represents
a
significant
advancement
in
immunotherapy,
especially
for
treating
solid
tumors
where
traditional
CAR-T
therapies
face
limitations.
CAR-MΦ
offers
promising
approach
to
target
and
eradicate
tumor
cells
by
utilizing
macrophages’
phagocytic
antigen-presenting
abilities.
However,
challenges
such
as
the
complex
microenvironment
(TME),
variability
expression,
immune
suppression
limit
their
efficacy.
This
review
addresses
these
issues,
exploring
mechanisms
of
action,
optimal
construct
designs,
interactions
within
TME.
It
also
delves
into
ex
vivo
manufacturing
CAR-MΦ,
discussing
autologous
allogeneic
sources
importance
stringent
quality
control.
The
potential
synergies
integrating
with
existing
cancer
like
checkpoint
inhibitors
conventional
chemotherapeutics
are
examined
highlight
possible
enhanced
treatment
outcomes.
Furthermore,
regulatory
pathways
scrutinized
alongside
established
protocols
cells,
identifying
unique
considerations
essential
clinical
trials
market
approval.
Proposed
safety
monitoring
frameworks
aim
manage
adverse
events,
cytokine
release
syndrome,
crucial
patient
safety.
Consolidating
current
research
insights,
this
seeks
refine
therapeutic
applications,
overcome
barriers,
suggest
future
directions
transition
from
experimental
platforms
standard
care
options.
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: Feb. 20, 2025
Natural
Killer
(NK)
cells
hold
significant
promise
as
therapeutic
agents
in
immuno-oncology
due
to
their
ability
target
and
eliminate
cancerous
infected
without
causing
graft-versus-host
disease
or
cytokine
release
syndrome.
However,
the
limited
availability
of
robust,
scalable
methods
for
generating
clinical-grade
NK
remains
a
limiting
factor
broader
clinical
application.
Here
we
report
development
novel
feeder-cell-free
culture
system
optimized
producing
from
cord
blood-derived
CD34+
hematopoietic
stem
progenitor
(HSPCs).
Our
method
eliminates
need
feeder
while
achieving
high
yields
that
exhibit
unique
marker
expression
cytotoxic
functions.
Cord
blood
HSPCs
were
cultured
our
established
hDLL
4
generated
large
numbers
human
T
lymphoid
progenitors
(ProTcells)
7
days.
ProTcells
further
hDLL4-free,
cell
differentiation
supplemented
with
cytokines.
Following
7-
14-day
culture,
this
produced
highly
pure
populations
(>90%
CD3-CD56+).
Flow
mass
cytometric
analysis
confirmed
activating
receptors,
transcription
factors
(ID2,
T-bet)
molecules
(perforin,
granzyme
A/B),
all
essential
ProT-NK
functionality.
These
are
an
immature
state,
indicated
by
absence
maturation
markers
(CD16,
KIRs).
Functional
assays
demonstrated
these
capable
degranulation
cytokines
production
(TNFα)
upon
stimulation
K562
showed
cytotoxicity
against
superior
Peripheral
Blood
(PB)-NK.
In
NSG-Tg(hIL-15)
mice,
colonize
bone
marrow,
liver,
spleen
persist
mature
marrow
at
least
9
days
post-injection.
Compared
D21,
D14
was
functional
homing
potential.
vivo,
anti-tumor
assay
uses
subcutaneous
model
has
potential
cells.
ex
vivo
process
supports
yields,
reducing
dependency
on
mitigating
contamination
risks.
findings
demonstrate
feasibility
large,
isolated
readily
available
sources
offer
efficient
alternative
PB-NK
therapies.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: April 11, 2024
Chimeric
antigen
receptor
(CAR)
T
cell
therapy
has
transformed
cancer
immunotherapy.
However,
significant
challenges
limit
its
application
beyond
B
cell-driven
malignancies,
including
limited
clinical
efficacy,
high
toxicity,
and
complex
autologous
product
manufacturing.
Despite
efforts
to
improve
CAR
outcomes,
there
is
a
growing
interest
in
utilizing
alternative
immune
cells
develop
cells.
These
offer
several
advantages,
such
as
major
histocompatibility
(MHC)-independent
function,
tumor
microenvironment
(TME)
modulation,
increased
tissue
infiltration
capabilities.
Currently,
products
from
various
subtypes,
innate
cells,
hematopoietic
progenitor
even
exosomes
are
being
explored.
often
show
enhanced
antitumor
diminished
superior
penetration.
With
these
benefits
mind,
numerous
trials
underway
access
the
potential
of
innovative
This
review
aims
thoroughly
examine
challenges,
existing
insights
on
new
treatment.
Advances in medical diagnosis, treatment, and care (AMDTC) book series,
Journal Year:
2024,
Volume and Issue:
unknown, P. 391 - 418
Published: Aug. 28, 2024
Cancer
immunotherapy
has
emerged
as
a
revolutionary
approach
in
the
fight
against
cancer.
Unlike
traditional
treatments
like
chemotherapy
and
radiation,
harnesses
power
of
body's
own
immune
system
to
identify
destroy
cancer
cells.
promising
therapy,
but
limitations
specificity
control
hinder
its
full
potential.
Synthetic
gene
circuits
offer
address
these
challenges.
This
chapter
emphasizes
diverse
applications
synthetic
immunotherapy.
Additionally,
authors
discuss
advantages
AND
gate
for
minimizing
off-target
effects,
engineered
bacteria
targeted
tumour
manipulation,
T-cell
engineering
enhanced
anti-tumour
activity.
Ultimately,
therapies
are
not
mutually
exclusive.
While
proven
effectiveness
accessibility,
hold
immense
promise
personalized,
long-term
solutions.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: June 5, 2024
The
occurrence
of
ovarian
cancer
(OC)
is
a
major
factor
in
women’s
mortality
rates.
Despite
progress
medical
treatments,
like
new
drugs
targeting
homologous
recombination
deficiency,
survival
rates
for
OC
patients
are
still
not
ideal.
tumor
microenvironment
(TME)
includes
cells,
fibroblasts
linked
to
(CAFs),
immune-inflammatory
and
the
substances
these
cells
secrete,
along
with
non-cellular
components
extracellular
matrix
(ECM).
First,
TME
mainly
plays
role
inhibiting
growth
protecting
normal
cell
survival.
As
tumors
progress,
gradually
becomes
place
promote
progression.
Immune
have
attracted
much
attention
as
targets
immunotherapy.
checkpoint
inhibitor
(ICI)
therapy
has
potential
regulate
TME,
suppressing
factors
that
facilitate
advancement,
reactivating
immune
managing
growth,
extending
advanced
cancer.
This
review
presents
an
outline
current
studies
on
distinct
cellular
elements
within
detailing
their
main
functions
possible
signaling
pathways.
Additionally,
we
examine
immunotherapy
rechallenge
OC,
specific
emphasis
biological
reasons
behind
resistance
ICIs.