Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Окт. 6, 2022
As
the
essential
regulators
of
organ
fibrosis,
macrophages
undergo
marked
phenotypic
and
functional
changes
after
injury.
These
in
macrophage
phenotype
function
can
result
maladaptive
repair,
causing
chronic
inflammation
development
pathological
fibrosis.
Autophagy,
a
highly
conserved
lysosomal
degradation
pathway,
is
one
major
players
to
maintain
homeostasis
through
clearing
protein
aggregates,
damaged
organelles,
invading
pathogens.
Emerging
evidence
has
shown
that
autophagy
plays
an
role
polarization,
inflammation,
Because
high
heterogeneity
different
organs,
types
may
play
roles
Here,
we
review
current
understanding
fibrosis
highlight
potential
treatment
Finally,
important
unresolved
issues
this
field
are
briefly
discussed.
A
better
mechanisms
contribute
developing
novel
therapies
for
inflammatory
diseases
Journal of Hematology & Oncology,
Год журнала:
2022,
Номер
15(1)
Опубликована: Март 12, 2022
Abstract
Immune
checkpoint
molecules
are
promising
anticancer
targets,
among
which
therapeutic
antibodies
targeting
the
PD-1/PD-L1
pathway
have
been
widely
applied
to
cancer
treatment
in
clinical
practice
and
great
potential.
However,
this
is
greatly
limited
by
its
low
response
rates
certain
cancers,
lack
of
known
biomarkers,
immune-related
toxicity,
innate
acquired
drug
resistance,
etc.
Overcoming
these
limitations
would
significantly
expand
applications
blockade
improve
rate
survival
time
patients.
In
present
review,
we
first
illustrate
biological
mechanisms
immune
checkpoints
their
role
healthy
system
as
well
tumor
microenvironment
(TME).
The
inhibits
effect
T
cells
TME,
turn
regulates
expression
levels
PD-1
PD-L1
through
multiple
mechanisms.
Several
strategies
proposed
solve
anti-PD-1/PD-L1
treatment,
including
combination
therapy
with
other
standard
treatments,
such
chemotherapy,
radiotherapy,
targeted
therapy,
anti-angiogenic
immunotherapies
even
diet
control.
Downregulation
TME
via
pharmacological
or
gene
regulation
methods
improves
efficacy
treatment.
Surprisingly,
recent
preclinical
studies
shown
that
upregulation
also
blockade.
Immunotherapy
a
strategy
provides
novel
insight
into
applications.
This
review
aims
guide
development
more
effective
less
toxic
immunotherapies.
Immunity,
Год журнала:
2021,
Номер
54(12), С. 2701 - 2711
Опубликована: Дек. 1, 2021
Cytotoxic
T
cells
are
important
effectors
of
anti-tumor
immunity.
While
tumor
killing
is
ascribed
to
CD8+
cell
function,
pre-clinical
and
clinical
studies
have
identified
intra-tumoral
CD4+
that
possess
cytotoxic
programs
can
directly
kill
cancer
cells.
found
in
other
disease
settings
including
infection
autoimmunity.
Here,
we
review
the
phenotypic
functional
characteristics
non-cancer
contexts.
We
conduct
a
comparative
examination
cytolytic
mechanisms
across
states
synthesize
features
define
these
independent
context.
discuss
regulatory
driving
ontogeny
effector
function
evidence
for
relevance
cancer.
In
this
context,
highlight
gaps
understanding
biology
as
well
potential
use
immunotherapies
specific
cancers.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Март 1, 2023
Abstract
Spatial
transcriptomics
technologies
generate
gene
expression
profiles
with
spatial
context,
requiring
spatially
informed
analysis
tools
for
three
key
tasks,
clustering,
multisample
integration,
and
cell-type
deconvolution.
We
present
GraphST,
a
graph
self-supervised
contrastive
learning
method
that
fully
exploits
data
to
outperform
existing
methods.
It
combines
neural
networks
learn
informative
discriminative
spot
representations
by
minimizing
the
embedding
distance
between
adjacent
spots
vice
versa.
demonstrated
GraphST
on
multiple
tissue
types
technology
platforms.
achieved
10%
higher
clustering
accuracy
better
delineated
fine-grained
structures
in
brain
embryo
tissues.
is
also
only
can
jointly
analyze
slices
vertical
or
horizontal
integration
while
correcting
batch
effects.
Lastly,
superior
deconvolution
capture
niches
like
lymph
node
germinal
centers
exhausted
tumor
infiltrating
T
cells
breast
tissue.
Nature Reviews Drug Discovery,
Год журнала:
2023,
Номер
22(6), С. 496 - 520
Опубликована: Апрель 28, 2023
Single-cell
technologies,
particularly
single-cell
RNA
sequencing
(scRNA-seq)
methods,
together
with
associated
computational
tools
and
the
growing
availability
of
public
data
resources,
are
transforming
drug
discovery
development.
New
opportunities
emerging
in
target
identification
owing
to
improved
disease
understanding
through
cell
subtyping,
highly
multiplexed
functional
genomics
screens
incorporating
scRNA-seq
enhancing
credentialling
prioritization.
ScRNA-seq
is
also
aiding
selection
relevant
preclinical
models
providing
new
insights
into
mechanisms
action.
In
clinical
development,
can
inform
decision-making
via
biomarker
for
patient
stratification
more
precise
monitoring
response
progression.
Here,
we
illustrate
how
methods
being
applied
key
steps
discuss
ongoing
challenges
their
implementation
pharmaceutical
industry.
There
have
been
significant
recent
advances
development
remarkable
Ferran
colleagues
primarily
pipeline,
from
decision-making.
Ongoing
potential
future
directions
discussed.
Cancer Communications,
Год журнала:
2022,
Номер
42(10), С. 913 - 936
Опубликована: Сен. 8, 2022
Breast
cancer
is
the
most
common
worldwide.
The
occurrence
of
breast
associated
with
many
risk
factors,
including
genetic
and
hereditary
predisposition.
cancers
are
highly
heterogeneous.
Treatment
strategies
for
vary
by
molecular
features,
activation
human
epidermal
growth
factor
receptor
2
(HER2),
hormonal
receptors
(estrogen
[ER]
progesterone
[PR]),
gene
mutations
(e.g.,
1/2
[BRCA1/2]
phosphatidylinositol-4,5-bisphosphate
3-kinase
catalytic
subunit
alpha
[PIK3CA])
markers
immune
microenvironment
tumor-infiltrating
lymphocyte
[TIL]
programmed
death-ligand
1
[PD-L1]).
Early-stage
considered
curable,
which
local-regional
therapies
(surgery
radiotherapy)
cornerstone,
systemic
therapy
given
before
or
after
surgery
when
necessary.
Preoperative
neoadjuvant
therapy,
targeted
drugs
checkpoint
inhibitors,
has
become
standard
care
early-stage
HER2-positive
triple-negative
cancer,
followed
risk-adapted
post-surgical
strategies.
For
ER-positive
early
endocrine
5-10
years
essential.
Advanced
distant
metastases
currently
incurable.
Systemic
in
this
setting
include
agents,
such
as
CDK4/6
inhibitors
phosphoinositide
(PI3K)
hormone
receptor-positive
disease,
anti-HER2
poly(ADP-ribose)
polymerase
BRCA1/2
mutation
carriers
immunotherapy
part
disease.
Innovation
technologies
precision
medicine
may
guide
individualized
treatment
escalation
de-escalation
future.
In
review,
we
summarized
latest
scientific
information
discussed
future
perspectives
on
cancer.