Nature,
Год журнала:
2021,
Номер
596(7870), С. 126 - 132
Опубликована: Июль 21, 2021
Abstract
PD-1
blockade
unleashes
CD8
T
cells
1
,
including
those
specific
for
mutation-associated
neoantigens
(MANA),
but
factors
in
the
tumour
microenvironment
can
inhibit
these
cell
responses.
Single-cell
transcriptomics
have
revealed
global
dysfunction
programs
tumour-infiltrating
lymphocytes
(TIL).
However,
majority
of
TIL
do
not
recognize
antigens
2
and
little
is
known
about
transcriptional
MANA-specific
TIL.
Here,
we
identify
clones
using
MANA
functional
expansion
assay
3
neoadjuvant
anti-PD-1-treated
non-small
lung
cancers
(NSCLC).
We
use
their
receptors
as
a
‘barcode’
to
track
analyse
coupled
single-cell
RNA
sequencing
receptor
sequencing.
find
both
MANA-
virus-specific
TIL,
regardless
response,
MANA-,
influenza-
Epstein–Barr
each
unique
programs.
Despite
exposure
cognate
antigen,
express
an
incompletely
activated
cytolytic
program.
hallmark
tissue-resident
memory
(TRM)
cells,
low
levels
interleukin-7
(IL-7R)
are
functionally
less
responsive
(IL-7)
compared
with
influenza-specific
TRM
cells.
Compared
from
responding
tumours,
non-responding
tumours
markedly
lower
ligand-dependent
signalling,
largely
confined
HOBIT
high
subsets,
coordinately
upregulate
checkpoints,
killer
inhibitory
inhibitors
activation.
These
findings
provide
important
insights
overcoming
resistance
blockade.
European Journal of Immunology,
Год журнала:
2019,
Номер
49(10), С. 1457 - 1973
Опубликована: Окт. 1, 2019
These
guidelines
are
a
consensus
work
of
considerable
number
members
the
immunology
and
flow
cytometry
community.
They
provide
theory
key
practical
aspects
enabling
immunologists
to
avoid
common
errors
that
often
undermine
immunological
data.
Notably,
there
comprehensive
sections
all
major
immune
cell
types
with
helpful
Tables
detailing
phenotypes
in
murine
human
cells.
The
latest
techniques
applications
also
described,
featuring
examples
data
can
be
generated
and,
importantly,
how
analysed.
Furthermore,
tips,
tricks
pitfalls
avoid,
written
peer-reviewed
by
leading
experts
field,
making
this
an
essential
research
companion.
Nature Communications,
Год журнала:
2018,
Номер
9(1)
Опубликована: Июль 9, 2018
Abstract
Identifying
tumor
antigen-specific
T
cells
from
cancer
patients
has
important
implications
for
immunotherapy
diagnostics
and
therapeutics.
Here,
we
show
that
CD103
+
CD39
tumor-infiltrating
CD8
(CD8
TIL)
are
enriched
tumor-reactive
both
in
primary
metastatic
tumors.
This
TIL
subset
is
found
across
six
different
malignancies
displays
an
exhausted
tissue-resident
memory
phenotype.
TILs
have
a
distinct
T-cell
receptor
(TCR)
repertoire,
with
clones
expanded
the
but
present
at
low
frequencies
periphery.
also
efficiently
kill
autologous
MHC-class
I-dependent
manner.
Finally,
higher
of
head
neck
associated
better
overall
survival.
Our
data
thus
describe
approach
detecting
will
help
define
mechanisms
existing
treatments,
may
lead
to
future
adoptive
therapies.
Frontiers in Immunology,
Год журнала:
2019,
Номер
10
Опубликована: Фев. 4, 2019
Chimeric
antigen
receptor
(CAR)
T
cells,
cells
that
have
been
genetically
engineered
to
express
a
recognizes
specific
antigen,
given
rise
breakthroughs
in
treating
hematological
malignancies.
However,
their
success
solid
tumors
has
limited.
The
unique
challenges
posed
CAR
cell
therapy
by
can
be
described
three
steps:
finding,
entering,
and
surviving
the
tumor.
use
of
dual
designs
recognize
multiple
antigens
at
once
local
administration
are
both
strategies
used
overcome
hurdle
localization
Additionally,
immunosuppressive
tumor
microenvironment
implications
for
function
terms
differentiation
exhaustion,
combining
CARs
with
checkpoint
blockade
or
depletion
other
suppressive
factors
shown
very
promising
results
mitigate
phenomenon
exhaustion.
Finally,
identifying
overcoming
mechanisms
associated
dysfunction
is
vital
importance
generating
proliferate
successfully
eliminate
cells.
structure
costimulatory
domains
chosen
may
play
an
important
role
overall
TME,
"armored"
secrete
cytokines
third-
fourth-generation
offer
ways
enhance
function.
