Cancer Cell,
Journal Year:
2023,
Volume and Issue:
41(11), P. 1852 - 1870.e9
Published: Oct. 12, 2023
Neoadjuvant
immune
checkpoint
blockade
(ICB)
demonstrates
promise
in
operable
esophageal
squamous
cell
carcinoma
(ESCC),
but
lacks
available
efficacy
biomarkers.
Here,
we
perform
single-cell
RNA-sequencing
of
tumors
from
patients
with
ESCC
undergoing
neoadjuvant
ICB,
revealing
a
subset
exhausted
CD8+
T
cells
expressing
SPRY1
(CD8+
Tex-SPRY1)
that
displays
progenitor
(Tpex)
phenotype
and
correlates
complete
response
to
ICB.
We
validate
Tex-SPRY1
as
an
ICB-specific
predictor
improved
survival
using
independent
ICB-/non-ICB
cohorts
demonstrate
expression
enforces
Tpex
enhances
ICB
efficacy.
Additionally,
contribute
proinflammatory
macrophages
functional
state
B
cells,
which
thereby
promotes
antitumor
immunity
by
enhancing
effector
functions.
Overall,
our
findings
unravel
progenitor-like
cells'
role
effective
responses
for
inform
mechanistic
biomarkers
future
individualized
immunotherapy.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: March 17, 2023
Abstract
Chronic
kidney
disease
(CKD)
is
estimated
to
affect
10–14%
of
global
population.
Kidney
fibrosis,
characterized
by
excessive
extracellular
matrix
deposition
leading
scarring,
a
hallmark
manifestation
in
different
progressive
CKD;
However,
at
present
no
antifibrotic
therapies
against
CKD
exist.
fibrosis
identified
tubule
atrophy,
interstitial
chronic
inflammation
and
fibrogenesis,
glomerulosclerosis,
vascular
rarefaction.
Fibrotic
niche,
where
organ
initiates,
complex
interplay
between
injured
parenchyma
(like
tubular
cells)
multiple
non-parenchymal
cell
lineages
(immune
mesenchymal
located
spatially
within
scarring
areas.
Although
the
mechanisms
are
complicated
due
kinds
cells
involved,
with
help
single-cell
technology,
many
key
questions
have
been
explored,
such
as
what
kind
renal
tubules
profibrotic,
myofibroblasts
originate,
which
immune
how
communicate
each
other.
In
addition,
genetics
epigenetics
deeper
that
regulate
fibrosis.
And
reversible
nature
epigenetic
changes
including
DNA
methylation,
RNA
interference,
chromatin
remodeling,
gives
an
opportunity
stop
or
reverse
therapeutic
strategies.
More
marketed
(e.g.,
RAS
blockage,
SGLT2
inhibitors)
developed
delay
progression
recent
years.
Furthermore,
better
understanding
also
favored
discover
biomarkers
fibrotic
injury.
review,
we
update
advances
mechanism
summarize
novel
treatment
for
CKD.
Annual Review of Pathology Mechanisms of Disease,
Journal Year:
2022,
Volume and Issue:
18(1), P. 123 - 148
Published: Sept. 21, 2022
Pancreatic
ductal
adenocarcinoma
(PDAC)
features
a
prominent
stromal
microenvironment
with
remarkable
cellular
and
spatial
heterogeneity
that
meaningfully
impacts
disease
biology
treatment
resistance.
Recent
advances
in
tissue
imaging
capabilities,
single-cell
analytics,
modeling
have
shed
light
on
organizing
principles
shape
the
complexity
of
PDAC
tumors.
These
insights
into
functional
dependencies
coordinate
cancer
cell
relationships
exist
between
cells
extracellular
matrix
components
present
tumors
are
expected
to
unveil
therapeutic
vulnerabilities.
We
review
recent
field
discuss
current
understandings
mechanisms
by
which
tumor
shapes
pathogenesis
therapy
Cell,
Journal Year:
2023,
Volume and Issue:
186(2), P. 363 - 381.e19
Published: Jan. 1, 2023
Advanced
solid
cancers
are
complex
assemblies
of
tumor,
immune,
and
stromal
cells
characterized
by
high
intratumoral
variation.
We
use
highly
multiplexed
tissue
imaging,
3D
reconstruction,
spatial
statistics,
machine
learning
to
identify
cell
types
states
underlying
morphological
features
known
diagnostic
prognostic
significance
in
colorectal
cancer.
Quantitation
these
high-plex
marker
space
reveals
recurrent
transitions
from
one
tumor
morphology
the
next,
some
which
coincident
with
long-range
gradients
expression
oncogenes
epigenetic
regulators.
At
invasive
margin,
where
normal,
immune
compete,
T
suppression
involves
multiple
imaging
shows
that
seemingly
localized
2D
such
as
tertiary
lymphoid
structures
commonly
interconnected
have
graded
molecular
properties.
Thus,
while
cancer
genetics
emphasizes
importance
discrete
changes
state,
whole-specimen
large-scale
analogous
those
developing
tissues.
Nature,
Journal Year:
2023,
Volume and Issue:
616(7957), P. 563 - 573
Published: April 12, 2023
Abstract
B
cells
are
frequently
found
in
the
margins
of
solid
tumours
as
organized
follicles
ectopic
lymphoid
organs
called
tertiary
structures
(TLS)
1,2
.
Although
TLS
have
been
to
correlate
with
improved
patient
survival
and
response
immune
checkpoint
blockade
(ICB),
underlying
mechanisms
this
association
remain
elusive
Here
we
investigate
lung-resident
cell
responses
patients
from
TRACERx
421
(Tracking
Non-Small-Cell
Lung
Cancer
Evolution
Through
Therapy)
other
lung
cancer
cohorts,
a
recently
established
immunogenic
mouse
model
for
adenocarcinoma
3
We
find
that
both
human
adenocarcinomas
elicit
local
germinal
centre
tumour-binding
antibodies,
further
identify
endogenous
retrovirus
(ERV)
envelope
glycoproteins
dominant
anti-tumour
antibody
target.
ERV-targeting
amplified
by
ICB
humans
mice,
targeted
inhibition
KRAS(G12C)
model.
ERV-reactive
antibodies
exert
activity
extends
model,
ERV
expression
predicts
outcome
adenocarcinoma.
Finally,
effective
immunotherapy
requires
CXCL13-dependent
formation.
Conversely,
therapeutic
CXCL13
treatment
potentiates
immunity
synergizes
ICB.
Our
findings
provide
possible
mechanistic
basis
response.
