Immune
cells
infiltrating
tumors
can
have
important
impact
on
tumor
progression
and
response
to
therapy.
We
present
an
efficient
algorithm
simultaneously
estimate
the
fraction
of
cancer
immune
cell
types
from
bulk
gene
expression
data.
Our
method
integrates
novel
profiles
each
major
non-malignant
type
found
in
tumors,
renormalization
based
cell-type-specific
mRNA
content,
ability
consider
uncharacterized
possibly
highly
variable
types.
Feasibility
is
demonstrated
by
validation
with
flow
cytometry,
immunohistochemistry
single-cell
RNA-Seq
analyses
human
melanoma
colorectal
specimens.
Altogether,
our
work
not
only
improves
accuracy
but
also
broadens
scope
absolute
predictions
data,
provides
a
unique
experimental
benchmark
for
immunogenomics
research
(http://epic.gfellerlab.org).
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.
The
distribution
and
abundance
of
immune
cells,
particularly
T-cell
subsets,
play
pivotal
roles
in
cancer
immunology
therapy.
T
cells
have
many
subsets
with
specific
function
current
methods
are
limited
estimating
them,
thus,
a
method
for
predicting
comprehensive
is
urgently
needed
research.
Here,
Immune
Cell
Abundance
Identifier
(ImmuCellAI),
gene
set
signature-based
method,
introduced
precisely
the
24
cell
types
including
18
from
expression
data.
Performance
evaluation
on
both
sequencing
data
flow
cytometry
results
public
indicate
that
ImmuCellAI
can
estimate
superior
accuracy
to
other
especially
subsets.
Application
immunotherapy
datasets
reveals
dendritic
cytotoxic
T,
gamma
delta
significantly
higher
comparisons
on-treatment
versus
pre-treatment
responders
non-responders.
Meanwhile,
an
result-based
model
built
response
high
(area
under
curve
0.80-0.91).
These
demonstrate
powerful
unique
tumor
infiltration
estimation
prediction.
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.
