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.
British Journal of Cancer,
Год журнала:
2018,
Номер
118(1), С. 9 - 16
Опубликована: Янв. 1, 2018
Immune
checkpoint
inhibitors
(ICI)
targeting
CTLA-4
and
the
PD-1/PD-L1
axis
have
shown
unprecedented
clinical
activity
in
several
types
of
cancer
are
rapidly
transforming
practice
medical
oncology.
Whereas
cytotoxic
chemotherapy
small
molecule
('targeted
therapies')
largely
act
on
cells
directly,
immune
reinvigorate
anti-tumour
responses
by
disrupting
co-inhibitory
T-cell
signalling.
While
resistance
routinely
develops
patients
treated
with
conventional
therapies
targeted
therapies,
durable
suggestive
long-lasting
immunologic
memory
commonly
seen
large
subsets
ICI.
However,
initial
response
appears
to
be
a
binary
event,
most
non-responders
single-agent
ICI
therapy
progressing
at
rate
consistent
natural
history
disease.
In
addition,
late
relapses
now
emerging
longer
follow-up
trial
populations,
suggesting
emergence
acquired
resistance.
As
robust
biomarkers
predict
and/or
remain
elusive,
mechanisms
underlying
innate
(primary)
(secondary)
inferred
from
pre-clinical
studies
correlative
data.
Improved
understanding
molecular
(and
resistance)
may
not
only
identify
novel
predictive
prognostic
biomarkers,
but
also
ultimately
guide
optimal
combination/sequencing
clinic.
Here
we
review
data
identifying
inhibition.
FEBS Journal,
Год журнала:
2018,
Номер
285(16), С. 2944 - 2971
Опубликована: Апрель 11, 2018
The
chemokines
(or
chemotactic
cytokines)
are
a
large
family
of
small,
secreted
proteins
that
signal
through
cell
surface
G
protein‐coupled
heptahelical
chemokine
receptors.
They
best
known
for
their
ability
to
stimulate
the
migration
cells,
most
notably
white
blood
cells
(leukocytes).
Consequently,
play
central
role
in
development
and
homeostasis
immune
system,
involved
all
protective
or
destructive
inflammatory
responses.
Classically
viewed
as
inducers
directed
migration,
it
is
now
clear
can
variety
other
types
undirected
migratory
behavior,
such
haptotaxis,
chemokinesis,
haptokinesis,
addition
inducing
arrest
adhesion.
However,
receptors
on
leukocytes
do
more
than
just
direct
these
molecules
also
be
expressed
on,
regulate
biology
of,
many
nonleukocytic
types.
Chemokines
profoundly
affected
by
post‐translational
modification,
interaction
with
extracellular
matrix
(
ECM
),
binding
‘atypical’
localization
abundance.
This
guide
gives
broad
overview
receptor
families;
summarizes
complex
physical
interactions
occur
network;
and,
using
specific
examples,
discusses
general
principles
function,
focusing
particularly
leukocyte
migration.
Annual Review of Medicine,
Год журнала:
2018,
Номер
69(1), С. 301 - 318
Опубликована: Янв. 29, 2018
Antigen-specific
CD8
T
cells
are
central
to
the
control
of
chronic
infections
and
cancer,
but
persistent
antigen
stimulation
results
in
cell
exhaustion.
Exhausted
have
decreased
effector
function
proliferative
capacity,
partly
caused
by
overexpression
inhibitory
receptors
such
as
programmed
death
(PD)-1.
Blockade
PD-1
pathway
has
opened
a
new
therapeutic
avenue
for
reinvigorating
responses,
with
positive
outcomes
especially
patients
cancer.
Other
strategies
restore
exhausted
currently
under
evaluation—many
combination
PD-1-targeted
therapy.
comprise
heterogeneous
populations
unique
differentiation
functional
states.
A
subset
stem
cell–like
+
responsible
burst
after
therapy
been
recently
described.
greater
understanding
exhaustion
is
imperative
establish
rational
immunotherapeutic
interventions.
