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
Distant
metastasis
remains
the
major
cause
of
morbidity
for
breast
cancer.
Individuals
with
liver
or
brain
have
an
extremely
poor
prognosis
and
low
response
rates
to
anti-PD-1/L1
immune
checkpoint
therapy
compared
those
at
other
sites.
Therefore,
it
is
urgent
investigate
underlying
mechanism
resistance
develop
more
effective
immunotherapy
strategies
these
patients.
Using
single-cell
RNA
sequencing,
a
high-resolution
map
entire
tumor
ecosystem
based
on
44
473
cells
from
cancer
metastases
depicted.
Identified
by
canonical
markers
confirmed
multiplex
immunofluorescent
staining,
metastatic
features
remarkable
reprogramming
immunosuppressive
such
as
FOXP3+
regulatory
T
cells,
LAMP3+
tolerogenic
dendritic
CCL18+
M2-like
macrophages,
RGS5+
cancer-associated
fibroblasts,
LGALS1+
microglial
cells.
In
addition,
PD-1
PD-L1/2
are
barely
expressed
in
CD8+
cancer/immune/stromal
respectively.
Interactions
molecules
LAG3-LGALS3
TIGIT-NECTIN2
between
found
play
dominant
roles
escape.
summary,
this
study
dissects
intratumoral
heterogeneity
microenvironment
first
time,
providing
insights
into
most
appropriate
Cell,
Год журнала:
2023,
Номер
186(19), С. 4235 - 4251.e20
Опубликована: Авг. 21, 2023
Natural
killer
(NK)
cells
play
indispensable
roles
in
innate
immune
responses
against
tumor
progression.
To
depict
their
phenotypic
and
functional
diversities
the
microenvironment,
we
perform
integrative
single-cell
RNA
sequencing
analyses
on
NK
from
716
patients
with
cancer,
covering
24
cancer
types.
We
observed
heterogeneity
cell
composition
a
tumor-type-specific
manner.
Notably,
have
identified
group
of
tumor-associated
that
are
enriched
tumors,
show
impaired
anti-tumor
functions,
associated
unfavorable
prognosis
resistance
to
immunotherapy.
Specific
myeloid
subpopulations,
particular
LAMP3+
dendritic
cells,
appear
mediate
regulation
immunity.
Our
study
provides
insights
into
NK-cell-based
immunity
highlights
potential
clinical
utilities
subsets
as
therapeutic
targets.
Nature,
Год журнала:
2023,
Номер
616(7957), С. 563 - 573
Опубликована: Апрель 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.
