Frontiers in Immunology,
Journal Year:
2021,
Volume and Issue:
11
Published: Feb. 2, 2021
Tumor-specific
CD8+T
cells
are
exposed
to
persistent
antigenic
stimulation
which
induces
a
dysfunctional
state
called
"exhaustion."
Though
functioning
limit
damage
caused
by
immune
response,
T
cell
exhaustion
leads
attenuated
effector
function
whereby
cytotoxic
fail
control
tumor
progression
in
the
late
stage.
This
pathway
is
dynamic
process
from
activation
"progenitor
exhaustion"
through
"terminally
with
distinct
properties.
With
rapid
development
of
immunotherapy
via
enhancing
function,
new
studies
dissecting
mechanisms
and
identifying
specific
biomarkers
differentiation
during
exhaustion.
Further,
although
checkpoint
inhibitors
(ICIs)
have
achieved
great
success
clinical
practice,
most
patients
still
show
limited
efficacy
ICIs.
The
expansion
progenitor
exhausted
explained
ICIs
while
depletion
pool
transient
terminally
accounted
for
failure
monotherapy
context
exorbitant
burden.
Thus,
combination
strategies
urgent
be
utilized
based
on
reduction
burden
or
pool.
In
this
review,
we
aim
introduce
concept
homeostasis
activated
status
microenvironment,
present
recent
findings
implications
therapy.
Science,
Journal Year:
2022,
Volume and Issue:
375(6576)
Published: Jan. 6, 2022
Ectopic
lymphoid
aggregates,
termed
tertiary
structures
(TLSs),
are
formed
in
numerous
cancer
types,
and,
with
few
exceptions,
their
presence
is
associated
superior
prognosis
and
response
to
immunotherapy.
In
spite
of
presumed
importance,
the
triggers
that
lead
TLS
formation
tissue
contribution
these
intratumoral
immune
responses
remain
incompletely
understood.
Here,
we
discuss
present
knowledge
on
TLSs
cancer,
focusing
(i)
drivers
formation,
(ii)
function
antitumor
response,
(iii)
potential
as
therapeutic
targets
human
cancers.
Immunity,
Journal Year:
2019,
Volume and Issue:
51(6), P. 1028 - 1042.e4
Published: Dec. 1, 2019
Although
CD4+
T
cell
"help"
is
crucial
to
sustain
antiviral
immunity,
the
mechanisms
by
which
cells
regulate
CD8+
differentiation
during
chronic
infection
remain
elusive.
Here,
using
single-cell
RNA
sequencing,
we
show
that
responding
were
more
heterogeneous
than
previously
appreciated.
Importantly,
our
findings
uncovered
formation
of
a
CX3CR1-expressing
subset
exhibited
potent
cytolytic
function
and
was
required
for
viral
control.
Notably,
data
further
demonstrate
this
cytotoxic
critically
dependent
on
help
via
interleukin-21
(IL-21)
exploitation
developmental
pathway
could
be
used
therapeutically
enhance
killer
infiltrated
into
tumor.
These
uncover
additional
molecular
how
"CD4+
help"
regulates
persistent
have
implications
toward
optimizing
generation
protective
in
immunotherapy.
