Frontiers in Immunology,
Journal Year:
2021,
Volume and Issue:
12
Published: July 20, 2021
A
paradigm
shift
in
the
understanding
of
exhausted
CD8
+
T
cell
(T
ex
)
lineage
is
underway.
Originally
thought
to
be
a
uniform
population
that
progressively
loses
effector
function
response
persistent
antigen,
single-cell
analysis
has
now
revealed
composed
multiple
interconnected
subpopulations.
The
heterogeneity
within
comprised
immune
checkpoint
blockade
(ICB)
permissive
and
refractory
subsets
termed
stem-like
terminally
differentiated
cells,
respectively.
These
populations
occupy
distinct
peripheral
intratumoral
niches
are
characterized
by
transcriptional
processes
govern
transitions
between
states.
This
review
presents
key
findings
field
construct
an
updated
view
spatial,
transcriptional,
functional
anti-tumoral
.
emerging
insights
broadly
call
for
(re-)focusing
cancer
immunotherapies
center
on
driver
mechanism(s)
underlying
developmental
continuum
aimed
at
stabilizing
subsets.
Cancer Cell,
Journal Year:
2021,
Volume and Issue:
39(5), P. 649 - 661.e5
Published: March 12, 2021
Immune
checkpoint
blockade
(ICB)
results
in
durable
disease
control
a
subset
of
patients
with
advanced
renal
cell
carcinoma
(RCC),
but
mechanisms
driving
resistance
are
poorly
understood.
We
characterize
the
single-cell
transcriptomes
cancer
and
immune
cells
from
metastatic
RCC
before
or
after
ICB
exposure.
In
responders,
subsets
cytotoxic
T
express
higher
levels
co-inhibitory
receptors
effector
molecules.
Macrophages
treated
biopsies
shift
toward
pro-inflammatory
states
response
to
an
interferon-rich
microenvironment
also
upregulate
immunosuppressive
markers.
cells,
we
identify
bifurcation
into
two
subpopulations
differing
angiogenic
signaling
upregulation
programs
ICB.
Expression
signatures
for
evasion
associated
PBRM1
mutation
survival
primary
ICB-treated
RCC.
Our
findings
demonstrate
that
remodels
modifies
interplay
between
populations
critical
understanding
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2021,
Volume and Issue:
40(1)
Published: May 3, 2021
Abstract
Background
Unraveling
the
mystery
of
cell
death
is
one
most
fundamental
progresses
life
sciences
during
past
decades.
Regulated
(RCD)
or
programmed
(PCD)
not
only
essential
in
embryonic
development,
but
also
plays
an
important
role
occurrence
and
progression
diseases,
especially
cancers.
Escaping
hallmarks
cancer.
Main
body
Pyroptosis
inflammatory
usually
caused
by
microbial
infection,
accompanied
activation
inflammasomes
maturation
pro-inflammatory
cytokines
interleukin-1β
(IL-1β)
interleukin-18
(IL-18).
Gasdermin
family
proteins
are
executors
pyroptosis.
Cytotoxic
N-terminal
gasdermins
generated
from
caspases
granzymes
proteases
mediated
cleavage
gasdermin
oligomerizes
forms
pore
across
membrane,
leading
to
release
IL-1β,
IL-18.
exerts
tumor
suppression
function
evokes
anti-tumor
immune
responses.
Therapeutic
regimens,
including
chemotherapy,
radiotherapy,
targeted
therapy
therapy,
induce
pyroptosis
cancer,
which
potentiate
local
systemic
immunity.
On
other
hand,
normal
cells
attributes
side
effects
anti-cancer
therapies.
Conclusion
In
this
review,
we
focus
on
regulatory
mechanisms
suppressive
We
discuss
attribution
reprogramming
microenvironments
restoration
immunity
its
potential
application
cancer
therapy.
Frontiers in Immunology,
Journal Year:
2021,
Volume and Issue:
12
Published: July 20, 2021
A
paradigm
shift
in
the
understanding
of
exhausted
CD8
+
T
cell
(T
ex
)
lineage
is
underway.
Originally
thought
to
be
a
uniform
population
that
progressively
loses
effector
function
response
persistent
antigen,
single-cell
analysis
has
now
revealed
composed
multiple
interconnected
subpopulations.
The
heterogeneity
within
comprised
immune
checkpoint
blockade
(ICB)
permissive
and
refractory
subsets
termed
stem-like
terminally
differentiated
cells,
respectively.
These
populations
occupy
distinct
peripheral
intratumoral
niches
are
characterized
by
transcriptional
processes
govern
transitions
between
states.
This
review
presents
key
findings
field
construct
an
updated
view
spatial,
transcriptional,
functional
anti-tumoral
.
emerging
insights
broadly
call
for
(re-)focusing
cancer
immunotherapies
center
on
driver
mechanism(s)
underlying
developmental
continuum
aimed
at
stabilizing
subsets.
