Frontiers in Immunology,
Journal Year:
2019,
Volume and Issue:
10
Published: April 18, 2019
Myeloid-derived
suppressor
cells
(MDSCs)
contribute
to
the
induction
of
an
immune
suppressive/anergic,
tumor
permissive
environment.
MDSCs
act
as
immunosuppression
orchestrators
also
by
interacting
with
several
components
both
innate
and
adaptive
immunity.
Natural
killer
(NK)
are
lymphoid
functioning
primary
effector
immunity,
against
tumors
virus-infected
cells.
Apart
from
previously
described
anergy
hypo-functionality
NK
in
different
tumors,
cancer
patients
show
pro-angiogenic
phenotype
functions,
similar
decidual
We
termed
present
microenvironment:
“tumor
infiltrating
NK”
(TINKs),
peripheral
blood
associated
(TANKs).
The
contribution
regulating
cell
function
tumor-bearing
host
still
represent
a
poorly
explored
topic,
even
less
is
known
on
regulation
MDSCs.
Here,
we
review
whether
crosstalk
between
can
impact
onset,
angiogenesis
progression,
focusing
relevant
cellular
molecular
events.
propose
that
similarity
properties
MDSC
those
decisual
during
pregnancy
could
hint
possible
onco-fetal
origin
these
leukocytes.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2021,
Volume and Issue:
40(1)
Published: June 4, 2021
Abstract
The
cytotoxic
T-lymphocyte–associated
antigen
4
(CTLA-4)/B7
and
programmed
death
1
(PD-1)/
cell
death-ligand
(PD-L1)
are
two
most
representative
immune
checkpoint
pathways,
which
negatively
regulate
T
function
during
different
phases
of
T-cell
activation.
Inhibitors
targeting
CTLA-4/B7
PD1/PD-L1
pathways
have
revolutionized
immunotherapies
for
numerous
cancer
types.
Although
the
combined
anti-CTLA-4/B7
anti-PD1/PD-L1
therapy
has
demonstrated
promising
clinical
efficacy,
only
a
small
percentage
patients
receiving
or
experienced
prolonged
survival.
Regulation
expression
PD-L1
CTLA-4
significantly
impacts
treatment
effect.
Understanding
in-depth
mechanisms
interplays
could
help
identify
with
better
immunotherapy
responses
promote
their
care.
In
this
review,
regulation
is
discussed
at
levels
DNA,
RNA,
proteins,
as
well
indirect
biomarkers,
localization
within
cell,
drugs.
Specifically,
some
potential
drugs
been
developed
to
expressions
high
efficiency.
The Journal of Cell Biology,
Journal Year:
2019,
Volume and Issue:
218(10), P. 3171 - 3187
Published: Sept. 19, 2019
Protein
folding
is
inherently
error
prone,
especially
in
the
endoplasmic
reticulum
(ER).
Even
with
an
elaborate
network
of
molecular
chaperones
and
protein
facilitators,
misfolding
can
occur
quite
frequently.
To
maintain
homeostasis,
eukaryotes
have
evolved
a
series
quality-control
checkpoints.
When
secretory
pathway
pathways
fail,
stress
response
pathways,
such
as
unfolded
(UPR),
are
induced.
In
addition,
ER,
which
initial
hub
biogenesis
pathway,
triages
misfolded
proteins
by
delivering
substrates
to
proteasome
or
lysosome/vacuole
through
ER-associated
degradation
(ERAD)
ER-phagy.
Some
escape
ER
instead
selected
for
Golgi
quality
control.
These
targeted
after
retrieval
delivery
lysosome/vacuole.
Here,
we
discuss
how
these
guardian
function,
their
activities
intersect
upon
induction
UPR,
decisions
made
dispose
pathway.
Journal of Hematology & Oncology,
Journal Year:
2022,
Volume and Issue:
15(1)
Published: March 12, 2022
Abstract
Immune
checkpoint
molecules
are
promising
anticancer
targets,
among
which
therapeutic
antibodies
targeting
the
PD-1/PD-L1
pathway
have
been
widely
applied
to
cancer
treatment
in
clinical
practice
and
great
potential.
However,
this
is
greatly
limited
by
its
low
response
rates
certain
cancers,
lack
of
known
biomarkers,
immune-related
toxicity,
innate
acquired
drug
resistance,
etc.
Overcoming
these
limitations
would
significantly
expand
applications
blockade
improve
rate
survival
time
patients.
In
present
review,
we
first
illustrate
biological
mechanisms
immune
checkpoints
their
role
healthy
system
as
well
tumor
microenvironment
(TME).
The
inhibits
effect
T
cells
TME,
turn
regulates
expression
levels
PD-1
PD-L1
through
multiple
mechanisms.
Several
strategies
proposed
solve
anti-PD-1/PD-L1
treatment,
including
combination
therapy
with
other
standard
treatments,
such
chemotherapy,
radiotherapy,
targeted
therapy,
anti-angiogenic
immunotherapies
even
diet
control.
Downregulation
TME
via
pharmacological
or
gene
regulation
methods
improves
efficacy
treatment.
Surprisingly,
recent
preclinical
studies
shown
that
upregulation
also
blockade.
Immunotherapy
a
strategy
provides
novel
insight
into
applications.
This
review
aims
guide
development
more
effective
less
toxic
immunotherapies.
Journal of Clinical Investigation,
Journal Year:
2019,
Volume and Issue:
129(8), P. 3324 - 3338
Published: July 14, 2019
Glycosylation
of
immune
receptors
and
ligands,
such
as
T
cell
receptor
coinhibitory
molecules,
regulates
signaling
activation
surveillance.
However,
how
oncogenic
initiates
glycosylation
molecules
to
induce
immunosuppression
remains
unclear.
Here
we
show
that
IL-6-activated
JAK1
phosphorylates
programmed
death-ligand
1
(PD-L1)
Tyr112,
which
recruits
the
endoplasmic
reticulum-associated
N-glycosyltransferase
STT3A
catalyze
PD-L1
maintain
stability.
Targeting
IL-6
by
antibody
induced
synergistic
killing
effects
when
combined
with
anti-T
immunoglobulin
mucin-3
(anti-Tim-3)
therapy
in
animal
models.
A
positive
correlation
between
expression
was
also
observed
hepatocellular
carcinoma
patient
tumor
tissues.
These
results
identify
a
mechanism
regulating
initiation
suggest
combination
anti-IL-6
anti-Tim-3
an
effective
marker-guided
therapeutic
strategy.
