Journal of Experimental & Clinical Cancer Research,
Journal Year:
2018,
Volume and Issue:
37(1)
Published: Dec. 1, 2018
Abundant
evidence
shows
that
triple-negative
breast
cancer
(TNBC)
is
heterogeneous,
and
many
efforts
have
been
devoted
to
identifying
TNBC
subtypes
on
the
basis
of
genomic
profiling.
However,
few
studies
explored
classification
specifically
based
immune
signatures
may
facilitate
optimal
stratification
patients
responsive
immunotherapy.Using
four
publicly
available
genomics
datasets,
we
classified
immunogenomic
profiling
29
signatures.
Unsupervised
supervised
machine
learning
methods
were
used
perform
classification.We
identified
three
named
Immunity
High
(Immunity_H),
Medium
(Immunity_M),
Low
(Immunity_L)
demonstrated
this
was
reliable
predictable
by
analyzing
multiple
different
datasets.
Immunity_H
characterized
greater
cell
infiltration
anti-tumor
activities,
as
well
better
survival
prognosis
compared
other
subtypes.
Besides
signatures,
some
cancer-associated
pathways
hyperactivated
in
Immunity_H,
including
apoptosis,
calcium
signaling,
MAPK
PI3K-Akt
RAS
signaling.
In
contrast,
Immunity_L
presented
depressed
increased
activation
cycle,
Hippo
DNA
replication,
mismatch
repair,
adhesion
molecule
binding,
spliceosome,
adherens
junction
function,
pyrimidine
metabolism,
glycosylphosphatidylinositol
(GPI)-anchor
biosynthesis,
RNA
polymerase
pathways.
Furthermore,
a
gene
co-expression
subnetwork
centered
around
five
transcription
factor
(TF)
genes
(CORO1A,
STAT4,
BCL11B,
ZNF831,
EOMES)
significant
subtype
two
TF
(IRF8
SPI1)
characteristic
subtype.The
identification
has
potential
clinical
implications
for
treatment.
British Journal of Cancer,
Journal Year:
2018,
Volume and Issue:
118(1), P. 9 - 16
Published: Jan. 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.
Journal for ImmunoTherapy of Cancer,
Journal Year:
2020,
Volume and Issue:
8(1), P. e000337 - e000337
Published: March 1, 2020
Cells
succumbing
to
stress
via
regulated
cell
death
(RCD)
can
initiate
an
adaptive
immune
response
associated
with
immunological
memory,
provided
they
display
sufficient
antigenicity
and
adjuvanticity.
Moreover,
multiple
intracellular
microenvironmental
features
determine
the
propensity
of
RCD
drive
immunity.
Here,
we
provide
updated
operational
definition
immunogenic
(ICD),
discuss
key
factors
that
dictate
ability
dying
cells
response,
summarize
experimental
assays
are
currently
available
for
assessment
ICD
in
vitro
vivo,
formulate
guidelines
their
interpretation.
