Immunotherapy,
represented
by
immune
checkpoint
inhibitors
(ICI),
is
transforming
the
treatment
of
cancer.
However,
only
a
small
percentage
patients
show
response
to
ICI,
and
there
an
unmet
need
for
biomarkers
that
will
identify
who
are
more
likely
respond
immunotherapy.
The
fundamental
basis
ICI
immunogenicity
tumor,
which
primarily
determined
tumor
antigenicity
antigen
presentation
efficiency.
Here,
we
propose
method
measure
score
(TIGS),
combines
mutational
burden
(TMB)
expression
signature
processing
presenting
machinery
(APM).
In
both
correlation
with
pan-cancer
objective
rates
(ORR)
clinical
prediction
individual
patients,
TIGS
consistently
showed
improved
performance
compared
TMB
other
known
response.
This
study
suggests
effective
tumor-inherent
biomarker
ICI-response
prediction.
Nucleic Acids Research,
Journal Year:
2020,
Volume and Issue:
48(W1), P. W509 - W514
Published: May 17, 2020
Abstract
Tumor
progression
and
the
efficacy
of
immunotherapy
are
strongly
influenced
by
composition
abundance
immune
cells
in
tumor
microenvironment.
Due
to
limitations
direct
measurement
methods,
computational
algorithms
often
used
infer
cell
from
bulk
transcriptome
profiles.
These
estimated
infiltrate
populations
have
been
associated
with
genomic
transcriptomic
changes
tumors,
providing
insight
into
tumor–immune
interactions.
However,
such
investigations
on
large-scale
public
data
remain
challenging.
To
lower
barriers
for
analysis
complex
interactions,
we
significantly
improved
our
previous
web
platform
TIMER.
Instead
just
using
one
algorithm,
TIMER2.0
(http://timer.cistrome.org/)
provides
more
robust
estimation
infiltration
levels
The
Cancer
Genome
Atlas
(TCGA)
or
user-provided
profiles
six
state-of-the-art
algorithms.
four
modules
investigating
associations
between
infiltrates
genetic
clinical
features,
exploring
cancer-related
TCGA
cohorts.
Each
module
can
generate
a
functional
heatmap
table,
enabling
user
easily
identify
significant
multiple
cancer
types
simultaneously.
Overall,
server
comprehensive
visualization
functions
infiltrating
cells.
Annals of Oncology,
Journal Year:
2018,
Volume and Issue:
30(1), P. 44 - 56
Published: Nov. 1, 2018
Treatment
with
immune
checkpoint
blockade
(ICB)
agents
such
as
anti-programmed
cell
death
protein
1
(PD-1),
death-ligand
(PD-L1),
and/or
anti-cytotoxic
T-lymphocyte-associated
4
(CTLA-4)
can
result
in
impressive
response
rates
and
durable
disease
remission
but
only
a
subset
of
patients
cancer.
Expression
PD-L1
has
demonstrated
utility
selecting
for
to
ICB
proven
be
an
important
biomarker
patient
selection.
Tumor
mutation
burden
(TMB)
is
emerging
potential
biomarker.
However,
refinement
interpretation
contextualization
required.
Journal of Cellular Physiology,
Journal Year:
2018,
Volume and Issue:
234(6), P. 8509 - 8521
Published: Nov. 22, 2018
CD8+
cytotoxic
T
lymphocytes
(CTLs)
are
preferred
immune
cells
for
targeting
cancer.
During
cancer
progression,
CTLs
encounter
dysfunction
and
exhaustion
due
to
immunerelated
tolerance
immunosuppression
within
the
tumor
microenvironment
(TME),
with
all
favor
adaptive
immune-resistance.
Cancer-associated
fibroblasts
(CAFs),
macrophage
type
2
(M2)
cells,
regulatory
(Tregs)
could
make
immunologic
barriers
against
CD8
+
cell-mediated
antitumor
responses.
Thus,
needed
be
primed
activated
toward
effector
in
a
process
called
immunity
cycle
making
durable
efficient
The
cell
priming
is
directed
essentially
as
corroboration
work
between
of
innate
including
dendritic
(DCs)
natural
killer
(NK)
CD4
adoptive
immunity.
Upon
activation,
infiltrate
core
or
invading
site
(so-called
infiltrated-inflamed
[I-I]
TME)
take
essential
roles
killing
cells.
Exogenous
reactivation
and/or
can
possible
using
rational
immunotherapy
strategies.
increase
ratio
costimulatory
coinhibitory
mediators
checkpoint
blockade
(ICB)
approach.
Programmed
death-1
receptor
(PD-1)-ligand
(PD-L1)
CTL-associated
antigen
4
(CTLA-4)
receptors
that
targeted
relieving
renewing
their
priming,
respectively,
thereby
eliminating
antigen-expressing
Due
diverse
relation
Tregs,
Treg
activity
dampened
increasing
number
rescuing
functional
potential
induce
immunosensitivity
Journal of Hematology & Oncology,
Journal Year:
2020,
Volume and Issue:
13(1)
Published: Aug. 10, 2020
Abstract
In
recent
years,
cancer
immunotherapy
based
on
immune
checkpoint
inhibitors
(ICIs)
has
achieved
considerable
success
in
the
clinic.
However,
ICIs
are
significantly
limited
by
fact
that
only
one
third
of
patients
with
most
types
respond
to
these
agents.
The
induction
cell
death
mechanisms
other
than
apoptosis
gradually
emerged
as
a
new
treatment
strategy
because
tumors
harbor
innate
resistance
apoptosis.
date,
possibility
combining
two
modalities
not
been
discussed
systematically.
Recently,
few
studies
revealed
crosstalk
between
distinct
and
antitumor
immunity.
pyroptosis,
ferroptosis,
necroptosis
combined
showed
synergistically
enhanced
activity,
even
ICI-resistant
tumors.
Immunotherapy-activated
CD8+
T
cells
traditionally
believed
induce
tumor
via
following
main
pathways:
(i)
perforin-granzyme
(ii)
Fas-FasL.
identified
mechanism
which
suppress
growth
inducing
ferroptosis
provoked
review
relationship
system
activation.
Hence,
this
review,
we
summarize
knowledge
reciprocal
interaction
immunity
mechanisms,
particularly
necroptosis,
three
potentially
novel
immunogenic
death.
Because
evidence
is
derived
from
using
animal
models,
also
reviewed
related
bioinformatics
data
available
for
human
tissues
public
databases,
partially
confirmed
presence
interactions
activation
Nature Reviews Gastroenterology & Hepatology,
Journal Year:
2021,
Volume and Issue:
18(8), P. 525 - 543
Published: April 13, 2021
Hepatocellular
carcinoma
(HCC)
is
a
prevalent
disease
with
progression
that
modulated
by
the
immune
system.
Systemic
therapy
used
in
advanced
stage
and
until
2017
consisted
only
of
antiangiogenic
tyrosine
kinase
inhibitors
(TKIs).
Immunotherapy
checkpoint
has
shown
strong
anti-tumour
activity
subset
patients
combination
anti-PDL1
antibody
atezolizumab
VEGF-neutralizing
bevacizumab
or
will
soon
become
standard
care
as
first-line
for
HCC,
whereas
anti-PD1
agents
nivolumab
pembrolizumab
are
after
TKIs
several
regions.
Other
strategies
such
adoptive
T-cell
transfer,
vaccination
virotherapy
have
not
yet
demonstrated
consistent
clinical
activity.
Major
unmet
challenges
HCC
immunotherapy
discovery
validation
predictive
biomarkers,
advancing
treatment
to
earlier
stages
disease,
applying
liver
dysfunction
more
effective
combinatorial
sequential
approaches.
Combinations
other
systemic
local
treatments
perceived
most
promising
opportunities
some
already
under
evaluation
large-scale
trials.
This
Review
provides
up-to-date
information
on
best
use
currently
available
immunotherapies
therapeutic
development.
Immunotherapeutic
interventions
might
be
tools
hepatocellular
carcinoma.
carcinoma,
mechanisms
response
resistance,
Genome Medicine,
Journal Year:
2020,
Volume and Issue:
12(1)
Published: Feb. 26, 2020
Despite
growing
numbers
of
immune
checkpoint
blockade
(ICB)
trials
with
available
omics
data,
it
remains
challenging
to
evaluate
the
robustness
ICB
response
and
evasion
mechanisms
comprehensively.
To
address
these
challenges,
we
integrated
large-scale
data
biomarkers
on
published
trials,
non-immunotherapy
tumor
profiles,
CRISPR
screens
a
web
platform
TIDE
(http://tide.dfci.harvard.edu).
We
processed
for
over
33K
samples
in
188
cohorts
from
public
databases,
998
tumors
12
clinical
studies,
eight
that
identified
gene
modulators
anticancer
response.
Integrating
three
interactive
analysis
modules,
demonstrate
utility
reuse
hypothesis
generation,
biomarker
optimization,
patient
stratification.
Nature Medicine,
Journal Year:
2019,
Volume and Issue:
25(12), P. 1916 - 1927
Published: Dec. 1, 2019
Abstract
Immune-checkpoint
blockade
(ICB)
has
demonstrated
efficacy
in
many
tumor
types,
but
predictors
of
responsiveness
to
anti-PD1
ICB
are
incompletely
characterized.
In
this
study,
we
analyzed
a
clinically
annotated
cohort
patients
with
melanoma
(
n
=
144)
treated
ICB,
whole-exome
and
whole-transcriptome
sequencing
pre-treatment
tumors.
We
found
that
mutational
burden
as
predictor
response
was
confounded
by
subtype,
whereas
multiple
novel
genomic
transcriptomic
features
predicted
selective
response,
including
associated
MHC-I
MHC-II
antigen
presentation.
Furthermore,
previous
anti-CTLA4
exposure
different
compared
tumors
were
naive
suggesting
immune
effects
ICB.
Finally,
developed
parsimonious
models
integrating
clinical,
predict
intrinsic
resistance
individual
tumors,
validation
smaller
independent
cohorts
limited
the
availability
comprehensive
data.
Broadly,
present
framework
discover
predictive
build
therapeutic
response.
Advanced Science,
Journal Year:
2020,
Volume and Issue:
7(7)
Published: Feb. 11, 2020
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.