The Journal of Experimental Medicine,
Год журнала:
2018,
Номер
215(10), С. 2520 - 2535
Опубликована: Авг. 28, 2018
CD8+
T
cells
infiltrating
tumors
are
largely
dysfunctional,
but
whether
a
subset
maintains
superior
functionality
remains
ill
defined.
By
high-dimensional
single
cell
analysis
of
millions
from
53
individuals
with
lung
cancer,
we
defined
those
subsets
that
enriched
in
compared
cancer-free
tissues
and
blood.
Besides
exhausted
activated
cells,
identified
CXCR5+
TIM-3–
partial
phenotype,
while
retaining
gene
networks
responsible
for
stem-like
plasticity
cytotoxicity,
as
revealed
by
sequencing
the
whole
transcriptome.
Ex
vivo,
displayed
enhanced
self-renewal
multipotency
more
differentiated
were
polyfunctional.
Analysis
inhibitory
costimulatory
receptors
PD-1,
TIGIT,
CD27
possible
targets
immunotherapy.
We
thus
demonstrate
hierarchy
differentiation
context
exhaustion
human
cancer
similar
to
chronically
infected
mice,
which
is
further
shown
disappear
disease
progression.
During
chronic
viral
infections
and
in
cancer,
T
cells
become
dysfunctional,
a
state
known
as
cell
exhaustion.
Although
it
is
well
recognized
that
memory
CD8
account
for
the
persistence
of
immunity
after
acute
infection,
how
exhausted
persist
remains
less
clear.
Using
infection
with
lymphocytic
choriomeningitis
virus
clone
13
tumor
samples,
we
demonstrate
differentiate
into
TCF1high
more
TCF1low
population.
Virus-specific
cells,
which
resemble
follicular
helper
(TFH)
recall
better
than
do
act
progenitor
to
replenish
cells.
We
show
TCF1
both
necessary
sufficient
support
this
progenitor-like
subset,
whereas
cell-intrinsic
type
I
interferon
signaling
suppresses
their
differentiation.
Accordingly,
deficiency
led
loss
these
sharp
contraction
virus-specific
uncontrolled
viremia.
Mechanistically,
repressed
several
pro-exhaustion
factors
induced
Bcl6
promoted
fate.
propose
TCF1-Bcl6
axis
counteracts
repress
exhaustion
maintain
stemness,
critical
persistent
antiviral
responses
infection.
These
findings
provide
insight
requirements
immune
face
suggest
mechanisms
by
effective
cell-mediated
may
be
enhanced
during
cancer.
Immunity,
Год журнала:
2019,
Номер
51(6), С. 1028 - 1042.e4
Опубликована: Дек. 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.
Annual Review of Immunology,
Год журнала:
2022,
Номер
40(1), С. 413 - 442
Опубликована: Фев. 3, 2022
Germinal
centers
(GCs)
are
microanatomical
sites
of
B
cell
clonal
expansion
and
antibody
affinity
maturation.
Therein,
cells
undergo
the
Darwinian
process
somatic
diversification
affinity-driven
selection
immunoglobulins
that
produces
high-affinity
antibodies
essential
for
effective
humoral
immunity.
Here,
we
review
recent
developments
in
field
GC
biology,
primarily
as
it
pertains
to
GCs
induced
by
infection
or
immunization.
First,
summarize
phenotype
function
different
types
compose
GC,
focusing
on
cells.
Then,
cellular
molecular
bases
affinity-dependent
within
export
memory
plasma
Finally,
present
an
overview
emerging
dynamics,
how
post-GC
shapes
diversity
secreted
into
serum.
