Cancer Communications,
Journal Year:
2020,
Volume and Issue:
40(4), P. 135 - 153
Published: April 1, 2020
Abstract
Conventional
immunohistochemistry
(IHC)
is
a
widely
used
diagnostic
technique
in
tissue
pathology.
However,
this
associated
with
number
of
limitations,
including
high
inter‐observer
variability
and
the
capacity
to
label
only
one
marker
per
section.
This
review
details
various
highly
multiplexed
techniques
that
have
emerged
circumvent
these
constraints,
allowing
simultaneous
detection
multiple
markers
on
single
section
comprehensive
study
cell
composition,
cellular
functional
cell‐cell
interactions.
Among
techniques,
multiplex
Immunohistochemistry/Immunofluorescence
(mIHC/IF)
has
be
particularly
promising.
mIHC/IF
provides
high‐throughput
staining
standardized
quantitative
analysis
for
reproducible,
efficient
cost‐effective
studies.
immediate
potential
translational
research
clinical
practice,
era
cancer
immunotherapy.
Modern Pathology,
Journal Year:
2021,
Volume and Issue:
35(1), P. 23 - 32
Published: Oct. 5, 2021
Traditional
pathology
approaches
have
played
an
integral
role
in
the
delivery
of
diagnosis,
semi-quantitative
or
qualitative
assessment
protein
expression,
and
classification
disease.
Technological
advances
increased
focus
on
precision
medicine
recently
paved
way
for
development
digital
pathology-based
quantitative
pathologic
assessments,
namely
whole
slide
imaging
artificial
intelligence
(AI)–based
solutions,
allowing
us
to
explore
extract
information
beyond
human
visual
perception.
Within
field
immuno-oncology,
application
such
methodologies
drug
translational
research
created
invaluable
opportunities
deciphering
complex
pathophysiology
discovery
novel
biomarkers
targets.
With
increasing
number
treatment
options
available
any
given
disease,
practitioners
face
growing
challenge
selecting
most
appropriate
each
patient.
The
ever-increasing
utilization
AI-based
substantially
expands
our
understanding
tumor
microenvironment,
with
patient
stratification
selection
diagnostic
assays
supporting
identification
optimal
regimen
based
profiles.
This
review
provides
overview
limitations
around
implementing
methods
biomarker
discusses
how
AI
should
be
considered
current
landscape
medicine,
touching
challenges
this
technology
may
if
adopted
clinical
settings.
traditional
pathologists
delivering
accurate
diagnoses
assessing
companion
diagnostics
enhanced
precision,
reproducibility,
scale
by
AI-powered
analysis
tools.
Frontiers in Immunology,
Journal Year:
2020,
Volume and Issue:
11
Published: May 19, 2020
Growth/differentiation
factor-15
(GDF-15),
also
named
macrophage
inhibitory
cytokine-1,
is
a
divergent
member
of
the
transforming
growth
factor
β
superfamily.
While
physiological
expression
barely
detectable
in
most
somatic
tissues
humans,
GDF-15
abundant
placenta.
Elsewhere,
often
induced
under
stress
conditions,
seemingly
to
maintain
cell
and
tissue
homeostasis;
however,
moderate
increase
blood
levels
observed
with
age.
Highly
elevated
are
mostly
linked
pathological
conditions
including
inflammation,
myocardial
ischemia,
notably
cancer.
has
thus
been
widely
explored
as
biomarker
for
disease
prognosis.
Mechanistically,
induction
anorexia
via
brainstem-restricted
receptor
GFRAL
(glial
cell-derived
neurotrophic
[GDNF]
family
α-like)
well
documented.
have
become
attractive
targets
metabolic
intervention.
Still,
several
mediated
effects
(including
its
role
pregnancy)
difficult
explain
described
pathway.
Hence,
there
clear
need
better
understand
non-metabolic
GDF-15.
With
particular
emphasis
on
immunomodulatory
potential
this
review
discusses
roles
pregnancy
infarction,
autoimmune
disease,
specifically
Importantly,
strong
predictive
value
may
plausibly
be
immune-regulatory
function.
The
associations
mechanistic
data
support
hypothesis
that
acts
immune
checkpoint
an
emerging
target
cancer
immunotherapy.
Clinical Cancer Research,
Journal Year:
2020,
Volume and Issue:
27(5), P. 1236 - 1241
Published: Nov. 16, 2020
Abstract
Immune
checkpoint
inhibitors,
including
antibodies
that
block
programmed
cell
death
protein-1
(PD-1)
and
PD-L1,
have
transformed
the
management
of
many
cancers.
However,
majority
patients
primary
or
acquired
resistance
to
these
immunotherapies.
There
is
a
significant
unmet
need
for
predictive
biomarkers
can
reliably
identify
who
derive
clinically
meaningful
response
from
PD-1/PD-L1
blockade.
High
tumor
mutational
burden
(TMB-H)
has
shown
promise
as
biomarker
in
lung
cancer,
but
broad
applicability
TMB-H
across
all
solid
tumors
unclear.
The
FDA
approved
PD-1
inhibitor,
pembrolizumab,
therapy
with
TMB
equal
greater
than
10
mutations/megabase
measured
by
FoundationOne
CDx
assay.
This
approval
was
based
on
an
exploratory
analysis
KEYNOTE-158
study,
which
single-arm,
phase
II
multi-cohort
study
pembrolizumab
select,
previously
treated
advanced
tumors.
Here,
we
elucidate
caveats
using
universal
threshold
While
recognize
importance
this
other
pan-cancer
approvals,
several
questions
about
remain
unanswered.
In
perspective,
discuss
clinical
trial
evidence
area.
We
review
relationship
between
immune
microenvironment.
highlight
risks
extrapolating
limited
number
histologies
tumors,
propose
avenues
future
research.
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: March 19, 2020
Combined
PARP
and
immune
checkpoint
inhibition
has
yielded
encouraging
results
in
ovarian
cancer,
but
predictive
biomarkers
are
lacking.
We
performed
immunogenomic
profiling
highly
multiplexed
single-cell
imaging
on
tumor
samples
from
patients
enrolled
a
Phase
I/II
trial
of
niraparib
pembrolizumab
cancer
(NCT02657889).
identify
two
determinants
response;
mutational
signature
3
reflecting
defective
homologous
recombination
DNA
repair,
positive
score
as
surrogate
interferon-primed
exhausted
CD8
+
T-cells
the
microenvironment.
Presence
one
or
both
features
associates
with
an
improved
outcome
while
concurrent
absence
yields
no
responses.
Single-cell
spatial
analysis
reveals
prominent
interactions
PD-L1
macrophages
cells
mechanistic
response.
Furthermore,
extreme
responders
shows
differential
clustering
first,
harboring
genomic
PD-L2
amplification
second.
