Cancer Cell,
Journal Year:
2019,
Volume and Issue:
35(2), P. 238 - 255.e6
Published: Feb. 1, 2019
Highlights•Activated
T
cell
signatures/populations
drive
response
to
anti-PD-1-based
therapies•EOMES+CD69+CD45RO+
effector
memory
cells
are
associated
with
response•EOMES+CD69+CD45RO+
expression
is
longer
PFS
and
tumor
shrinkage•Non-responders
TIL-hot
tumors
express
other
immune
drug
targetsSummaryCancer
immunotherapies
provide
survival
benefits
in
responding
patients,
but
many
patients
fail
respond.
Identifying
the
biology
of
treatment
resistance
a
priority
optimize
selection
improve
patient
outcomes.
We
performed
transcriptomic
profiling
on
158
biopsies
from
melanoma
treated
anti-PD-1
monotherapy
(n
=
63)
or
combined
anti-CTLA-4
57).
These
data
identified
activated
signatures
populations
responders
both
treatments.
Further
mass
cytometry
analysis
an
EOMES+CD69+CD45RO+
phenotype
that
was
significantly
more
abundant
immunotherapy
compared
non-responders
18).
The
gene
profile
this
population
progression-free
single
agent
greater
shrinkage
treatments.Graphical
Abstract
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.
Annual Review of Pathology Mechanisms of Disease,
Journal Year:
2020,
Volume and Issue:
16(1), P. 223 - 249
Published: Nov. 16, 2020
Immune
checkpoint
inhibitors
(ICIs)
have
made
an
indelible
mark
in
the
field
of
cancer
immunotherapy.
Starting
with
approval
anti-cytotoxic
T
lymphocyte-associated
protein
4
(anti-CTLA-4)
for
advanced-stage
melanoma
2011,
ICIs-which
now
also
include
antibodies
against
programmed
cell
death
1
(PD-1)
and
its
ligand
(PD-L1)-quickly
gained
US
Food
Drug
Administration
treatment
a
wide
array
types,
demonstrating
unprecedented
extension
patient
survival.
However,
despite
success
ICIs,
resistance
to
these
agents
restricts
number
patients
able
achieve
durable
responses,
immune-related
adverse
events
complicate
treatment.
Thus,
better
understanding
requirements
effective
safe
antitumor
immune
response
following
ICI
therapy
is
needed.
Studies
both
tumoral
systemic
changes
system
yielded
insight
into
basis
efficacy
resistance.
Ultimately,
by
building
on
insights,
researchers
should
be
combine
ICIs
other
agents,
or
design
new
immunotherapies,
broader
more
as
well
greater
safety.
Here,
we
review
history
clinical
utility
mechanisms
therapy,
local
associated
outcome.
