Nature Biotechnology,
Journal Year:
2022,
Volume and Issue:
41(1), P. 60 - 69
Published: July 25, 2022
Extending
the
success
of
cellular
immunotherapies
against
blood
cancers
to
realm
solid
tumors
will
require
improved
in
vitro
models
that
reveal
therapeutic
modes
action
at
molecular
level.
Here
we
describe
a
system,
called
BEHAV3D,
developed
study
dynamic
interactions
immune
cells
and
patient
cancer
organoids
by
means
imaging
transcriptomics.
We
apply
BEHAV3D
live-track
>150,000
engineered
T
cultured
with
patient-derived,
solid-tumor
organoids,
identifying
'super
engager'
behavioral
cluster
comprising
potent
serial
killing
capacity.
Among
other
cell
concepts
also
metabolome-sensing
(TEGs)
detect
behavior-specific
gene
signatures
include
group
27
genes
no
previously
described
function
are
expressed
super
engager
killer
TEGs.
further
show
type
I
interferon
can
prime
resistant
for
TEG-mediated
killing.
is
promising
tool
characterization
behavioral-phenotypic
heterogeneity
may
support
optimization
personalized
solid-tumor-targeting
therapies.
Frontiers in Immunology,
Journal Year:
2020,
Volume and Issue:
11
Published: March 6, 2020
Colorectal
cancer
(CRC)
is
highly
heterogeneous
at
the
genetic
and
molecular
level,
which
has
major
repercussions
on
efficacy
of
immunotherapy.
A
small
subset
CRCs
exhibit
microsatellite
instability
(MSI),
a
indicator
defective
DNA
mismatch
repair
(MMR),
but
majority
are
microsatellite-stable
(MSS).
The
high
tumor
mutational
burden
(TMB)
neoantigen
load
in
MSI
tumors
favors
infiltration
immune
effector
cells,
antitumor
responses
within
these
strong
relative
to
their
MSS
counterparts.
emerged
as
predictive
marker
for
checkpoint
blockade
over
last
few
years
nivolumab
or
pembrolizumab
targeting
PD-1
been
approved
patients
with
refractory
metastatic
CRC.
However,
some
show
polymerase
epsilon
(POLE)
mutations
that
also
confer
very
TMB
may
be
heavily
infiltrated
by
cells
making
them
amenable
respond
inhibitors
(ICI).
In
this
review
we
discuss
role
different
landscapes
CRC
relationships
defined
subtypes.
We
potential
reasons
why
met
limited
success
patients,
despite
finding
cell
primary
non-metastatic
prognostic
factor
relapse
survival.
then
consider
ways
develop
mechanisms
resist
ICI.
Finally,
address
latest
advances
vaccination
how
personalized
vaccine
strategy
might
overcome
resistance
whom
not
treatment
option.
AJP Cell Physiology,
Journal Year:
2020,
Volume and Issue:
319(1), P. C151 - C165
Published: May 27, 2020
In
vitro
cell
cultures
are
crucial
research
tools
for
modeling
human
development
and
diseases.
Although
the
conventional
monolayer
have
been
widely
used
in
past,
lack
of
tissue
architecture
complexity
such
model
fails
to
inform
true
biological
processes
vivo.
Recent
advances
organoid
technology
revolutionized
culture
biomedical
by
creating
powerful
three-dimensional
(3D)
models
recapitulate
cellular
heterogeneity,
structure,
functions
primary
tissues.
Such
enables
researchers
recreate
organs
diseases
a
dish
thus
holds
great
promises
many
translational
applications
as
regenerative
medicine,
drug
discovery,
precision
medicine.
this
review,
we
provide
an
overview
history
development.
We
discuss
strengths
limitations
organoids
well
their
potential
laboratory
clinic.
Genes & Development,
Journal Year:
2021,
Volume and Issue:
35(11-12), P. 787 - 820
Published: June 1, 2021
Colorectal
cancer
has
served
as
a
genetic
and
biological
paradigm
for
the
evolution
of
solid
tumors,
these
insights
have
illuminated
early
detection,
risk
stratification,
prevention,
treatment
principles.
Employing
hallmarks
framework,
we
provide
conceptual
framework
to
understand
how
alterations
in
colorectal
drive
cell
biology
properties
shape
heterotypic
interactions
across
cells
tumor
microenvironment.
This
review
details
research
advances
pertaining
genetics
cancer,
emerging
concepts
gleaned
from
immune
single-cell
profiling,
critical
remaining
knowledge
gaps
influencing
development
effective
therapies
this
that
remains
major
public
health
burden.
Cell Reports,
Journal Year:
2020,
Volume and Issue:
31(11), P. 107762 - 107762
Published: June 1, 2020
There
remains
an
unmet
need
for
preclinical
models
to
enable
personalized
therapy
ovarian
cancer
(OC)
patients.
Here
we
evaluate
the
capacity
of
patient-derived
organoids
(PDOs)
predict
clinical
drug
response
and
functional
consequences
tumor
heterogeneity.
We
included
36
whole-genome-characterized
PDOs
from
23
OC
patients
with
known
histories.
maintain
genomic
features
original
lesion
recapitulate
patient
neoadjuvant
carboplatin/paclitaxel
combination
treatment.
display
inter-
intrapatient
heterogeneity
chemotherapy
targeted
drugs,
which
can
be
partially
explained
by
genetic
aberrations.
PDO
screening
identifies
high
responsiveness
at
least
one
88%
are
valuable
that
provide
insights
into
individual
OC,
complementary
testing.
Generating
multiple
locations
improve
decision
making
increase
our
knowledge
Cell Reports,
Journal Year:
2020,
Volume and Issue:
31(5), P. 107588 - 107588
Published: May 1, 2020
Clinical
implementation
of
tumor
organoids
for
personalized
medicine
requires
that
pure
can
be
reliably
established.
Here,
we
present
our
experience
with
organoid
cultures
from
>70
non-small
cell
lung
cancer
(NSCLC)
samples.
We
systematically
evaluate
several
methods
to
identify
purity
established
intrapulmonary
tumors.
Eighty
percent
lesions
have
a
normal
copy
number
profile,
suggesting
overgrowth
by
airway
(AOs).
This
is
further
supported
the
failure
detect
mutations
found
in
original
organoids.
Histomorphology
alone
insufficient
determine
purity,
but
when
combined
p63
immunostaining,
and
AOs
distinguished.
Taking
into
account
AOs,
establishment
rate
NSCLC
17%.
Therefore,
current
are
establish
lesions.
discourage
their
use
unless
steps
taken
prevent
AOs.
