Frontiers in Immunology,
Год журнала:
2020,
Номер
11
Опубликована: Ноя. 5, 2020
Cancer
immunotherapy
with
antibodies
targeting
the
programmed
cell
death
1
protein
(PD-1)/
ligand
(PD-L1)
axis
have
changed
standard
of
care
in
multiple
cancers.
However,
durable
antitumor
responses
been
observed
only
a
minority
patients,
indicating
presence
other
inhibitory
mechanisms
that
act
to
restrain
anticancer
immunity.
Therefore,
new
therapeutic
strategies
targeted
against
immune
suppressive
are
needed
enhance
immunity
and
maximize
clinical
benefit
cancer
patients
who
resistant
checkpoint
inhibition.
Preclinical
studies
identified
abnormalities
tumor
microenvironment
(TME)
can
thwart
efficacy
PD-1/PD-L1
blockade.
Angiogenic
factors
such
as
vascular
endothelial
growth
factor
(VEGF)
drive
immunosuppression
TME
by
inducing
abnormalities,
suppressing
antigen
presentation
effector
cells,
or
augmenting
activity
regulatory
T
myeloid-derived
suppressor
tumor-associated
macrophages.
In
turn,
immunosuppressive
cells
angiogenesis,
thereby
creating
vicious
cycle
suppressed
VEGF-mediated
suppression
its
negative
impact
on
provide
rationale
combine
anti-VEGF
drugs
normalize
TME.
A
multitude
trials
initiated
evaluate
combinations
antibody
an
variety
Recently,
positive
results
from
five
Phase
III
non-small
lung
(adenocarcinoma),
renal
carcinoma,
hepatocellular
carcinoma
shown
agents
significantly
improved
outcomes
compared
respective
standards
care.
Such
approved
health
authorities
now
treatment
options
for
cancer,
carcinoma.
plethora
randomized
similar
currently
ongoing.
Here
we
discuss
principle
studied
preclinical
models
part
translational
studies.
We
also
data
recently
reported
trials.
Finally,
how
these
concepts
approaches
be
further
incorporated
into
practice
improve
cancer.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Март 29, 2021
Abstract
Currently,
pyroptosis
has
received
more
and
attention
because
of
its
association
with
innate
immunity
disease.
The
research
scope
expanded
the
discovery
gasdermin
family.
A
great
deal
evidence
shows
that
can
affect
development
tumors.
relationship
between
tumors
is
diverse
in
different
tissues
genetic
backgrounds.
In
this
review,
we
provide
basic
knowledge
pyroptosis,
explain
tumors,
focus
on
significance
tumor
treatment.
addition,
further
summarize
possibility
as
a
potential
treatment
strategy
describe
side
effects
radiotherapy
chemotherapy
caused
by
pyroptosis.
brief,
double-edged
sword
for
rational
use
dual
effect
will
help
us
explore
formation
ideas
patients
to
develop
new
drugs
based
Journal of Clinical Oncology,
Год журнала:
2020,
Номер
38(26), С. 2960 - 2970
Опубликована: Июль 27, 2020
PURPOSE
The
immunomodulatory
effect
of
lenvatinib
(a
multikinase
inhibitor)
on
tumor
microenvironments
may
contribute
to
antitumor
activity
when
combined
with
programmed
death
receptor-1
(PD-1)
signaling
inhibitors
in
hepatocellular
carcinoma
(HCC).
We
report
results
from
a
phase
Ib
study
plus
pembrolizumab
(an
anti–PD-1
antibody)
unresectable
HCC
(uHCC).
PATIENTS
AND
METHODS
In
this
open-label
multicenter
study,
patients
uHCC
received
(bodyweight
≥
60
kg,
12
mg;
<
8
mg)
orally
daily
and
200
mg
intravenously
day
1
21-day
cycle.
included
dose-limiting
toxicity
(DLT)
an
expansion
(first-line
patients).
Primary
objectives
were
safety/tolerability
(DLT
phase),
objective
response
rate
(ORR)
duration
(DOR)
by
modified
RECIST
(mRECIST)
version
1.1
(v1.1)
per
independent
imaging
review
(IIR;
phase).
RESULTS
A
total
104
enrolled.
No
DLTs
reported
(n
=
6)
the
DLT
phase;
100
(expansion
n
2
phase)
had
no
prior
systemic
therapy
Barcelona
Clinic
Liver
Cancer
stage
B
29)
or
C
disease
71).
At
data
cutoff,
37%
remained
treatment.
Median
follow-up
was
10.6
months
(95%
CI,
9.2
11.5
months).
Confirmed
ORRs
IIR
46.0%
36.0%
56.3%)
mRECIST
26.6%
46.2%)
v1.1.
DORs
8.6
6.9
not
estimable
[NE])
12.6
NE)
progression-free
survival
9.3
overall
22
months.
Grade
3
treatment-related
adverse
events
occurred
67%
(grade
5,
3%)
patients.
new
safety
signals
identified.
CONCLUSION
Lenvatinib
has
promising
uHCC.
Toxicities
manageable,
unexpected
signals.
Nature,
Год журнала:
2021,
Номер
592(7854), С. 450 - 456
Опубликована: Март 24, 2021
Abstract
Hepatocellular
carcinoma
(HCC)
can
have
viral
or
non-viral
causes
1–5
.
Non-alcoholic
steatohepatitis
(NASH)
is
an
important
driver
of
HCC.
Immunotherapy
has
been
approved
for
treating
HCC,
but
biomarker-based
stratification
patients
optimal
response
to
therapy
unmet
need
6,7
Here
we
report
the
progressive
accumulation
exhausted,
unconventionally
activated
CD8
+
PD1
T
cells
in
NASH-affected
livers.
In
preclinical
models
NASH-induced
therapeutic
immunotherapy
targeted
at
programmed
death-1
(PD1)
expanded
within
tumours
did
not
lead
tumour
regression,
which
indicates
that
immune
surveillance
was
impaired.
When
given
prophylactically,
anti-PD1
treatment
led
increase
incidence
NASH–HCC
and
number
size
nodules,
correlated
with
increased
hepatic
CXCR6
,
TOX
TNF
cells.
The
HCC
triggered
by
prevented
depletion
neutralization,
suggesting
help
induce
NASH–HCC,
rather
than
invigorating
executing
surveillance.
We
found
similar
phenotypic
functional
profiles
from
humans
NAFLD
NASH.
A
meta-analysis
three
randomized
phase
III
clinical
trials
tested
inhibitors
PDL1
(programmed
death-ligand
1)
more
1,600
advanced
revealed
improve
survival
two
additional
cohorts,
NASH-driven
who
received
anti-PDL1
showed
reduced
overall
compared
other
aetiologies.
Collectively,
these
data
show
particularly
might
be
less
responsive
immunotherapy,
probably
owing
NASH-related
aberrant
cell
activation
causing
tissue
damage
leads
impaired
Our
provide
a
rationale
according
underlying
aetiology
studies
as
primary
adjuvant
treatment.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Фев. 23, 2021
Abstract
The
current
treatment
strategies
in
advanced
malignancies
remain
limited.
Notably,
immunotherapies
have
raised
hope
for
a
successful
control
of
these
diseases,
but
their
therapeutic
responses
are
suboptimal
and
vary
considerably
among
individuals.
Tumor-associated
macrophages
(TAMs)
major
component
the
tumor
microenvironment
(TME)
often
correlated
with
poor
prognosis
therapy
resistance,
including
immunotherapies.
Thus,
deeper
understanding
complex
roles
TAMs
immunotherapy
regulation
could
provide
new
insight
into
TME.
Furthermore,
targeting
is
an
emerging
field
interest
due
to
that
will
synergize
In
this
review,
we
summarize
recent
studies
investigating
involvement
immune
checkpoint
inhibition,
vaccines
adoptive
cell
transfer
therapies,
discuss
potential
as
adjuvant
