Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: July 25, 2022
Despite
the
promise
of
immune
checkpoint
inhibition
(ICI),
therapeutic
responses
remain
limited.
This
raises
possibility
that
standard
care
treatments
delivered
in
concert
may
compromise
tumor
response.
To
address
this,
we
employ
tobacco-signature
head
and
neck
squamous
cell
carcinoma
murine
models
which
map
tumor-draining
lymphatics
develop
for
regional
lymphablation
with
surgery
or
radiation.
We
find
eliminates
ICI
response,
worsening
overall
survival
repolarizing
tumor-
peripheral-immune
compartments.
Mechanistically,
within
lymphatics,
observe
an
upregulation
conventional
type
I
dendritic
cells
interferon
signaling
show
both
are
necessary
response
lost
lymphablation.
Ultimately,
provide
a
mechanistic
understanding
how
oncologic
therapies
targeting
impact
to
immune-oncology
therapy
order
define
rational,
lymphatic-preserving
treatment
sequences
mobilize
systemic
antitumor
immunity,
achieve
optimal
responses,
control
metastatic
disease,
confer
durable
immunity.
Cell Reports,
Journal Year:
2020,
Volume and Issue:
31(3), P. 107523 - 107523
Published: April 1, 2020
Recently
developed
approaches
for
highly
multiplexed
imaging
have
revealed
complex
patterns
of
cellular
positioning
and
cell-cell
interactions
with
important
roles
in
both
cellular-
tissue-level
physiology.
However,
tools
to
quantitatively
study
patterning
tissue
architecture
are
currently
lacking.
Here,
we
develop
a
spatial
analysis
toolbox,
the
histo-cytometric
multidimensional
pipeline
(CytoMAP),
which
incorporates
data
clustering,
positional
correlation,
dimensionality
reduction,
2D/3D
region
reconstruction
identify
localized
networks
reveal
features
organization.
We
apply
CytoMAP
microanatomy
innate
immune
subsets
murine
lymph
nodes
(LNs)
mutually
exclusive
segregation
migratory
dendritic
cells
(DCs),
regionalized
compartmentalization
SIRPα
Cancer Cell,
Journal Year:
2020,
Volume and Issue:
37(6), P. 786 - 799.e5
Published: June 1, 2020
Generation
of
tumor-infiltrating
lymphocytes
begins
when
tumor
antigens
reach
the
lymph
node
(LN)
to
stimulate
T
cells,
yet
we
know
little
how
material
is
disseminated
among
large
variety
antigen-presenting
dendritic
cell
(DC)
subsets
in
LN.
Here,
demonstrate
that
proteins
are
carried
LN
within
discrete
vesicles
inside
DCs
and
then
transferred
DC
subsets.
A
synapse
formed
between
interacting
vesicle
transfer
takes
place
absence
free
exosomes.
-containing
can
uniquely
activate
whereas
lacking
them
do
not.
Understanding
this
restricted
sharing
identity
provides
substantial
room
for
engineering
better
anti-tumor
immunity.
Nature Communications,
Journal Year:
2019,
Volume and Issue:
10(1)
Published: July 4, 2019
Recent
advances
in
optical
clearing
and
light-sheet
microscopy
have
provided
unprecedented
access
to
structural
molecular
information
from
intact
tissues.
However,
current
microscopes
imposed
constraints
on
the
size,
shape,
number
of
specimens,
compatibility
with
various
protocols.
Here
we
present
a
multi-immersion
open-top
microscope
that
enables
simple
mounting
multiple
specimens
processed
variety
protocols,
which
will
facilitate
wide
adoption
by
preclinical
researchers
clinical
laboratories.
In
particular,
geometry
provides
unsurpassed
versatility
interface
range
accessory
technologies
future.
Proceedings of the National Academy of Sciences,
Journal Year:
2020,
Volume and Issue:
117(52), P. 33455 - 33465
Published: Dec. 21, 2020
The
diverse
composition
of
mammalian
tissues
poses
challenges
for
understanding
the
cell-cell
interactions
required
organ
homeostasis
and
how
spatial
relationships
are
perturbed
during
disease.
Existing
methods
such
as
single-cell
genomics,
lacking
a
context,
traditional
immunofluorescence,
capturing
only
two
to
six
molecular
features,
cannot
resolve
these
issues.
Imaging
technologies
have
been
developed
address
problems,
but
each
possesses
limitations
that
constrain
widespread
use.
Here
we
report
method
overcomes
major
impediments
highly
multiplex
tissue
imaging.
"Iterative
bleaching
extends
multiplexity"
(IBEX)
uses
an
iterative
staining
chemical
enable
high-resolution
imaging
>65
parameters
in
same
section
without
physical
degradation.
IBEX
can
be
employed
with
various
types
conventional
microscopes
permits
use
both
commercially
available
user-generated
antibodies
"open"
system
allow
easy
adjustment
panels
based
on
ongoing
marker
discovery
efforts.
We
show
also
used
amplified
strongly
fixed
limited
epitope
retention
oligonucleotide-based
staining,
allowing
potential
cross-referencing
between
flow
cytometry,
cellular
indexing
transcriptomes
epitopes
by
sequencing,
analysis
tissue.
To
facilitate
data
processing,
provide
open-source
platform
automated
registration
images.
thus
represents
technology
rapidly
integrated
into
most
current
laboratory
workflows
achieve
high-content
reveal
complex
landscape
organs
tissues.
