Annual Review of Immunology,
Год журнала:
2022,
Номер
40(1), С. 45 - 74
Опубликована: Апрель 26, 2022
The
transformative
success
of
antibodies
targeting
the
PD-1
(programmed
death
1)/B7-H1
(B7
homolog
1)
pathway
(anti-PD
therapy)
has
revolutionized
cancer
treatment.
However,
only
a
fraction
patients
with
solid
tumors
and
some
hematopoietic
malignancies
respond
to
anti-PD
therapy,
reason
for
failure
in
other
is
less
known.
By
dissecting
mechanisms
underlying
this
resistance,
current
studies
reveal
that
tumor
microenvironment
major
location
resistance
occur.
Furthermore,
appear
be
highly
heterogeneous.
Here,
we
discuss
recent
human
data
identifying
therapy.
We
review
evidence
immune-based
such
as
loss
neoantigens,
defects
antigen
presentation
interferon
signaling,
immune
inhibitory
molecules,
exclusion
T
cells.
also
clinical
emerging
alterations
metabolism,
microbiota,
epigenetics.
Finally,
strategies
overcome
therapy
emphasize
need
develop
additional
immunotherapies
based
on
concept
normalization
immunotherapy.
Cell,
Год журнала:
2023,
Номер
186(8), С. 1729 - 1754
Опубликована: Апрель 1, 2023
Pancreatic
ductal
adenocarcinoma
(PDAC)
remains
one
of
the
deadliest
cancers.
Significant
efforts
have
largely
defined
major
genetic
factors
driving
PDAC
pathogenesis
and
progression.
tumors
are
characterized
by
a
complex
microenvironment
that
orchestrates
metabolic
alterations
supports
milieu
interactions
among
various
cell
types
within
this
niche.
In
review,
we
highlight
foundational
studies
driven
our
understanding
these
processes.
We
further
discuss
recent
technological
advances
continue
to
expand
complexity.
posit
clinical
translation
research
endeavors
will
enhance
currently
dismal
survival
rate
recalcitrant
disease.
CA A Cancer Journal for Clinicians,
Год журнала:
2021,
Номер
71(4), С. 333 - 358
Опубликована: Май 13, 2021
Abstract
Cancer
has
myriad
effects
on
metabolism
that
include
both
rewiring
of
intracellular
to
enable
cancer
cells
proliferate
inappropriately
and
adapt
the
tumor
microenvironment,
changes
in
normal
tissue
metabolism.
With
recognition
fluorodeoxyglucose‐positron
emission
tomography
imaging
is
an
important
tool
for
management
many
cancers,
other
metabolites
biological
samples
have
been
spotlight
diagnosis,
monitoring,
therapy.
Metabolomics
global
analysis
small
molecule
like
‐omics
technologies
can
provide
critical
information
about
state
are
otherwise
not
apparent.
Here,
authors
review
how
therapies
interact
with
at
cellular
systemic
levels.
An
overview
metabolomics
provided
a
focus
currently
available
they
applied
clinical
translational
research
setting.
The
also
discuss
could
be
further
leveraged
future
improve
patients
cancer.
Journal of Clinical Investigation,
Год журнала:
2020,
Номер
130(7), С. 3865 - 3884
Опубликована: Апрель 23, 2020
Myeloid
cells
comprise
a
major
component
of
the
tumor
microenvironment
(TME)
that
promotes
growth
and
immune
evasion.
By
employing
small-molecule
inhibitor
glutamine
metabolism,
not
only
were
we
able
to
inhibit
growth,
but
markedly
inhibited
generation
recruitment
myeloid-derived
suppressor
(MDSCs).
Targeting
metabolism
led
decrease
in
CSF3
hence
MDSCs
as
well
immunogenic
cell
death,
leading
an
increase
inflammatory
tumor-associated
macrophages
(TAMs).
Alternatively,
inhibiting
themselves
activation-induced
death
conversion
macrophages.
Surprisingly,
blocking
also
IDO
expression
both
cells,
marked
kynurenine
levels.
This
turn
development
metastasis
further
enhanced
antitumor
immunity.
Indeed,
targeting
rendered
checkpoint
blockade-resistant
tumors
susceptible
immunotherapy.
Overall,
our
studies
define
intimate
interplay
between
unique
suppressive
cells.