Journal of Experimental & Clinical Cancer Research,
Journal Year:
2022,
Volume and Issue:
41(1)
Published: April 7, 2022
Cholangiocarcinoma
(CCA)
is
the
second
most
common
primary
liver
cancer
and
associated
with
a
dismal
prognosis
due
to
lack
of
an
efficient
systemic
therapy.
In
contrast
other
cancers,
new
immunotherapies
have
demonstrated
unsatisfactory
results
in
clinical
trials,
underlining
importance
deeper
understanding
special
tumor
microenvironment
CCA
role
immune
cells
interacting
tumor.
Tumor-infiltrating
lymphocytes
(TILs)
are
important
component
adaptive
system
foundation
current
immunotherapy.
Therefore,
aim
this
review
summarize
literature
focusing
on
proportions
distribution,
molecular
pathogenesis,
prognostic
significance
TILs
their
immunotherapy
for
patients.In
CCA,
CD8+
CD4+
T
represent
majority
mostly
sequestered
around
cells.
CD20+
B
Natural
Killer
(NK)
less
frequent.
contrast,
Foxp3+
(regulatory
cells,
Tregs)
observed
infiltrate
into
stromal
such
as
TAMs,
TANs,
MSDCs
CAFs
inhibit
protection
function
by
secreting
factors
like
IL-10
TGF-β.
With
respect
Wnt/-catenin,
TGF-signaling
routes,
aPKC-i/P-Sp1/Snail
Signaling,
B7-H1/PD-1Pathway
Fas/FasL
signaling
pathways
connected
malignant
potential
contributed
evasion
increasing
TIL
apoptosis.
Distinct
subtypes
show
different
implications
long-term
outcome
CCA.
Although
there
occasionally
conflicting
results,
positively
correlated
oncological
while
high
number
Tregs
very
likely
worse
overall
survival.
also
play
major
CCA.In
summary,
presence
may
marker
target
novel
therapy,
but
more
translationaldata
needed
fully
unravel
treatment
Nature,
Journal Year:
2021,
Volume and Issue:
592(7854), P. 450 - 456
Published: March 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.
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,
JAMA Oncology,
Journal Year:
2020,
Volume and Issue:
7(1), P. 113 - 113
Published: Oct. 22, 2020
For
more
than
a
decade,
sorafenib
has
been
the
only
systemic
treatment
option
for
patients
with
advanced
hepatocellular
carcinoma
(HCC).
However,
rapid
progress
over
past
few
years
led
to
approval
of
other
angiogenesis
inhibitors
and
several
immune
checkpoint
blockers
(ICBs)
that
have
added
armamentarium
HCC.
Moreover,
recent
success
combination
bevacizumab
atezolizumab
signals
an
important
change
in
front-line
HCC.This
review
summarizes
rapidly
emerging
clinical
data
on
promise
challenges
implementing
ICBs
HCC
discusses
unmet
need
biomarkers
predict
response
or
resistance
therapy.
Two
strategies
target
immunosuppression
tumors
are
also
discussed:
one
proven
(vascular
endothelial
growth
factor
pathway
inhibition)
currently
under
investigation
(transforming
factor-β
inhibition).
The
rationale
preliminary
evidence
how
their
inhibition
may
reprogram
immunosuppressive
milieu
enhance
efficacy
reviewed.The
successes
failures
ICBs,
alone
combination,
provided
insights
into
implement
this
novel
therapy
new
avenues
immunotherapy
disease.
