Abstract
Cancer
immunotherapies
that
engage
immune
cells
to
fight
against
tumors
are
proving
be
powerful
weapons
in
combating
cancer
and
becoming
increasingly
utilized
the
clinics.
However,
for
majority
of
patients
with
solid
tumors,
little
or
no
progress
has
been
seen,
presumably
due
lack
adequate
approaches
can
reprogram
local
immunosuppressive
tumor
milieu
thus
reinvigorate
antitumor
immunity.
Tumor-associated
macrophages
(TAMs),
which
abundantly
infiltrate
most
could
contribute
progression
by
stimulating
proliferation,
angiogenesis,
metastasis,
providing
a
barrier
Initial
TAMs-targeting
strategies
have
shown
efficacy
across
therapeutic
modalities
types
both
preclinical
clinical
studies.
TAMs-targeted
roughly
divided
into
those
deplete
TAMs
modulate
activities.
We
here
reviewed
mechanisms
become
compromise
TAMs-focused
also
summarized.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Июль 12, 2021
Abstract
Cancer
development
and
its
response
to
therapy
are
regulated
by
inflammation,
which
either
promotes
or
suppresses
tumor
progression,
potentially
displaying
opposing
effects
on
therapeutic
outcomes.
Chronic
inflammation
facilitates
progression
treatment
resistance,
whereas
induction
of
acute
inflammatory
reactions
often
stimulates
the
maturation
dendritic
cells
(DCs)
antigen
presentation,
leading
anti-tumor
immune
responses.
In
addition,
multiple
signaling
pathways,
such
as
nuclear
factor
kappa
B
(NF-kB),
Janus
kinase/signal
transducers
activators
transcription
(JAK-STAT),
toll-like
receptor
(TLR)
cGAS/STING,
mitogen-activated
protein
kinase
(MAPK);
factors,
including
cytokines
(e.g.,
interleukin
(IL),
interferon
(IFN),
necrosis
(TNF)-α),
chemokines
C-C
motif
chemokine
ligands
(CCLs)
C-X-C
(CXCLs)),
growth
factors
vascular
endothelial
(VEGF),
transforming
(TGF)-β),
inflammasome;
well
metabolites
prostaglandins,
leukotrienes,
thromboxane,
specialized
proresolving
mediators
(SPM),
have
been
identified
pivotal
regulators
initiation
resolution
inflammation.
Nowadays,
local
irradiation,
recombinant
cytokines,
neutralizing
antibodies,
small-molecule
inhibitors,
DC
vaccines,
oncolytic
viruses,
TLR
agonists,
SPM
developed
specifically
modulate
in
cancer
therapy,
with
some
these
already
undergoing
clinical
trials.
Herein,
we
discuss
crosstalk
between
processes.
We
also
highlight
potential
targets
for
harnessing
cancer.
Journal of Hematology & Oncology,
Год журнала:
2019,
Номер
12(1)
Опубликована: Июль 12, 2019
Tumor
metastasis
is
a
major
contributor
to
the
death
of
cancer
patients.
It
driven
not
only
by
intrinsic
alterations
in
tumor
cells,
but
also
implicated
cross-talk
between
cells
and
their
altered
microenvironment
components.
Tumor-associated
macrophages
(TAMs)
are
key
that
create
an
immunosuppressive
(TME)
producing
cytokines,
chemokines,
growth
factors,
triggering
inhibitory
immune
checkpoint
proteins
release
T
cells.
In
doing
so,
TAMs
exhibit
important
functions
facilitating
metastatic
cascade
and,
meanwhile,
provide
multiple
targets
certain
blockade
immunotherapies
for
opposing
progression.
this
article,
we
summarize
regulating
networks
TAM
polarization
mechanisms
underlying
TAM-facilitated
metastasis.
Based
on
overview
current
experimental
evidence
dissecting
critical
roles
metastasis,
discuss
prospect
potential
applications
TAM-focused
therapeutic
strategies
clinical
treatment
at
present
future.
Cancer Discovery,
Год журнала:
2021,
Номер
11(4), С. 933 - 959
Опубликована: Апрель 1, 2021
Abstract
Strategies
to
therapeutically
target
the
tumor
microenvironment
(TME)
have
emerged
as
a
promising
approach
for
cancer
treatment
in
recent
years
due
critical
roles
of
TME
regulating
progression
and
modulating
response
standard-of-care
therapies.
Here,
we
summarize
current
knowledge
regarding
most
advanced
TME-directed
therapies,
which
either
been
clinically
approved
or
are
currently
being
evaluated
trials,
including
immunotherapies,
antiangiogenic
drugs,
treatments
directed
against
cancer-associated
fibroblasts
extracellular
matrix.
We
also
discuss
some
challenges
associated
with
future
perspectives
this
evolving
field.
Significance:
This
review
provides
comprehensive
analysis
therapies
targeting
TME,
combining
discussion
underlying
basic
biology
clinical
evaluation
different
therapeutic
approaches,
highlighting
perspectives.
