American Society of Clinical Oncology Educational Book,
Journal Year:
2019,
Volume and Issue:
39, P. 165 - 174
Published: May 1, 2019
Emerging
immunotherapeutic
approaches
have
revolutionized
the
treatment
of
multiple
malignancies.
Immune
checkpoint
blockers
(ICBs)
enabled
never-before-seen
success
rates
in
durable
tumor
control
and
enhanced
survival
benefit
patients
with
advanced
cancers.
However,
this
effect
is
not
universal,
resulting
responder
nonresponder
populations
only
between,
but
also
within
solid
types.
Although
ICBs
are
thought
to
be
most
effective
against
tumors
more
genetic
mutations
higher
antigen
loads,
always
case
for
all
cancers
or
a
cancer
subtype.
Furthermore,
debilitating
sometimes
deadly
immune-related
adverse
events
(irAEs)
resulted
from
aberrant
activation
T-cell
responses
following
immunotherapy.
Thus,
we
must
identify
new
ways
overcome
resistance
ICB-based
immunotherapies
limit
irAEs.
In
fact,
preclinical
clinical
data
identified
abnormalities
microenvironment
(TME)
that
can
thwart
efficacy
such
as
ICBs.
Here,
will
discuss
how
reprogramming
various
facets
TME
(blood
vessels,
myeloid
cells,
regulatory
T
cells
[Tregs])
may
TME-instigated
mechanisms
We
applications
strategic
approach,
including
recent
successful
phase
III
trial
combining
bevacizumab
atezolizumab
chemotherapy
metastatic
nonsquamous
non-small
cell
lung
led
rapid
approval
by
U.S.
Food
Drug
Administration
regimen
first-line
treatment.
Given
accelerated
testing
combined
targeted
therapies
larger
numbers
cancer,
these
concepts
incorporated
into
practice
improve
immunotherapy
outcomes.
Immune Network,
Journal Year:
2014,
Volume and Issue:
14(6), P. 277 - 277
Published: Jan. 1, 2014
T
cells
are
central
players
in
the
regulation
of
adaptive
immunity
and
immune
tolerance.In
periphery,
cell
differentiation
for
maturation
effector
function
is
regulated
by
a
number
factors.Various
factors
such
as
antigens,
co-stimulation
signals,
cytokines
regulate
into
functionally
specialized
regulatory
cells.Other
nutrients,
micronutrients,
nuclear
hormones
microbial
products
provide
important
environmental
cues
differentiation.A
mounting
body
evidence
indicates
that
metabolites
shortchain
fatty
acids
(SCFAs)
have
profound
effects
on
directly
indirectly
their
differentiation.We
review
current
status
our
understanding
SCFA
functions
peripheral
activity
discuss
impact
tissue
inflammation.
Journal of Clinical Investigation,
Journal Year:
2016,
Volume and Issue:
126(1), P. 23 - 31
Published: Jan. 3, 2016
Sepsis
is
a
systemic
inflammatory
response
induced
by
an
infection,
leading
to
organ
dysfunction
and
mortality.
Historically,
sepsis-induced
lethality
were
attributed
the
interplay
between
antiinflammatory
responses.
With
advances
in
intensive
care
management
goal-directed
interventions,
early
sepsis
mortality
has
diminished,
only
surge
later
after
"recovery"
from
acute
events,
prompting
search
for
alterations
immune
function.
well
known
alter
innate
adaptive
responses
sustained
periods
clinical
"recovery,"
with
immunosuppression
being
prominent
example
of
such
alterations.
Recent
studies
have
centered
on
immune-modulatory
therapy.
These
efforts
are
focused
defining
reversing
persistent
cell
that
associated
long
events
resolved.
Immunity,
Journal Year:
2019,
Volume and Issue:
50(2), P. 493 - 504.e7
Published: Feb. 1, 2019
Non-lymphoid
tissues
(NLTs)
harbor
a
pool
of
adaptive
immune
cells
with
largely
unexplored
phenotype
and
development.
We
used
single-cell
RNA-seq
to
characterize
35,000
CD4+
regulatory
(Treg)
memory
(Tmem)
T
in
mouse
skin
colon,
their
respective
draining
lymph
nodes
(LNs)
spleen.
In
these
tissues,
we
identified
Treg
cell
subpopulations
distinct
degrees
NLT
phenotype.
Subpopulation
pseudotime
ordering
gene
kinetics
were
consistent
recruitment
yet
the
initial
NLT-priming
LNs
final
stages
functional
adaptation
reflected
tissue-specific
differences.
Predicted
recapitulated
using
an
vivo
melanoma-induction
model,
validating
key
regulators
receptors.
Finally,
profiled
human
blood
Tmem
cells,
cross-mammalian
conserved
tissue
signatures.
summary,
describe
relationship
between
heterogeneity
NLTs
through
combined
use
computational
prediction
validation.
