OncoImmunology,
Journal Year:
2024,
Volume and Issue:
13(1)
Published: June 14, 2024
Conventional
type
1
dendritic
cells
(cDC1)
are
critical
regulators
of
anti-tumoral
T-cell
responses.
The
structure
and
abundance
intercellular
contacts
between
cDC1
CD8
T
in
cancer
tissues
is
important
to
determine
the
outcome
response.
However,
molecular
determinants
controlling
stability
cDC1–CD8
interactions
during
progression
remain
poorly
investigated.
Here,
we
generated
a
genetic
model
non-small
cell
lung
crossed
fluorescent
reporter
(KP-XCR1venus)
allow
detection
cDC1-CD8T
clusters
tumor
across
stages.
We
found
that
cDC1-CD8
abundant
productive
at
early
stages
development
but
progressively
diminish
advanced
tumors.
Transcriptional
profiling
flow
cytometry
identified
adhesion
molecule
ALCAM/CD166
(Activated
Leukocyte
Cell
Adhesion
Molecule,
ligand
CD6)
as
highly
expressed
by
significantly
downregulated
Analysis
human
datasets
indicated
ALCAM
its
expression
correlates
better
prognosis.
Mechanistically,
triggering
on
induces
cytoskeletal
remodeling
contact
formation
whereas
blockade
prevents
activation.
Together,
our
results
indicate
stabilize
stages,
while
loss
tumors
contributes
immune
evasion.
Nature,
Journal Year:
2024,
Volume and Issue:
629(8011), P. 417 - 425
Published: April 24, 2024
Abstract
Cancer-specific
TCF1
+
stem-like
CD8
T
cells
can
drive
protective
anticancer
immunity
through
expansion
and
effector
cell
differentiation
1–4
;
however,
this
response
is
dysfunctional
in
tumours.
Current
cancer
immunotherapies
2,5–9
promote
responses
some
but
not
all
patients.
This
variation
points
towards
currently
ill-defined
mechanisms
that
limit
cell-mediated
immunity.
Here
we
demonstrate
tumour-derived
prostaglandin
E2
(PGE
2
)
restricts
the
proliferative
of
within
tumours,
which
promotes
immune
escape.
PGE
does
affect
priming
draining
lymph
nodes.
acts
EP
4
(EP
/EP
receptor
signalling
to
intratumoural
generation
early
late
populations
originate
from
tumour-infiltrating
lymphocytes
(TILs).
Ablation
cancer-specific
rescues
their
tumours
leads
tumour
elimination
multiple
mouse
models.
Mechanistically,
suppression
interleukin-2
(IL-2)
pathway
underlies
-mediated
inhibition
TIL
responses.
Altogether,
uncover
a
key
mechanism
IL-2
responsiveness
TILs
prevents
these
cells.
study
identifies
–EP
axis
as
molecular
target
restore
achieve
control.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Oct. 18, 2024
Immunotherapy
has
made
significant
strides
in
cancer
treatment,
particularly
through
immune
checkpoint
blockade
(ICB),
which
shown
notable
clinical
benefits
across
various
tumor
types.
Despite
the
transformative
impact
of
ICB
treatment
therapy,
only
a
minority
patients
exhibit
positive
response
to
it.
In
with
solid
tumors,
those
who
respond
well
typically
demonstrate
an
active
profile
referred
as
"hot"
(immune-inflamed)
phenotype.
On
other
hand,
non-responsive
may
distinct
"cold"
(immune-desert)
phenotype,
differing
from
features
tumors.
Additionally,
there
is
more
nuanced
"excluded"
positioned
between
and
categories,
known
type.
Effective
differentiation
understanding
intrinsic
factors,
characteristics,
TME,
external
factors
are
critical
for
predicting
results.
It
widely
accepted
that
therapy
exerts
profound
effect
on
limited
efficacy
against
or
"altered"
necessitating
combinations
therapeutic
modalities
enhance
cell
infiltration
into
tissue
convert
tumors
ones.
Therefore,
aligning
traits
this
review
systematically
delineates
respective
influencing
extensively
discusses
varied
approaches
drug
targets
based
assess
efficacy.
Science,
Journal Year:
2024,
Volume and Issue:
386(6719)
Published: Sept. 5, 2024
Immunotherapy
can
lead
to
long-term
survival
for
some
cancer
patients,
yet
generalized
success
has
been
hampered
by
insufficient
antigen
presentation
and
exclusion
of
immunogenic
cells
from
the
tumor
microenvironment.
Here,
we
developed
an
approach
reprogram
in
vivo
adenoviral
delivery
transcription
factors
PU.1,
IRF8,
BATF3,
which
enabled
them
present
antigens
as
type
1
conventional
dendritic
cells.
Reprogrammed
remodeled
their
microenvironment,
recruited,
expanded
polyclonal
cytotoxic
T
cells;
induced
regressions;
established
systemic
immunity
multiple
mouse
melanoma
models.
In
human
spheroids
xenografts,
reprogramming
dendritic-like
progressed
independently
immunosuppression,
usually
limits
immunotherapy.
Our
study
paves
way
clinical
trials
immune
cell
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Nov. 24, 2023
Atezolizumab
(anti-PD-L1)
combined
with
bevacizumab
(anti-VEGFA)
is
the
first-line
immunotherapy
for
advanced
hepatocellular
carcinoma
(HCC),
but
number
of
patients
who
benefit
from
this
regimen
remains
limited.
Here,
we
combine
dual
PD-L1
and
VEGFA
blockade
(DPVB)
low-dose
radiotherapy
(LDRT),
which
rapidly
inflames
tumors,
rendering
them
vulnerable
to
immunotherapy.
The
combinatorial
therapy
exhibits
superior
antitumor
efficacy
mediated
by
CD8+
T
cells
in
various
preclinical
HCC
models.
Treatment
relies
upon
mobilizing
exhausted-like
(CD8+
Tex)
effector
function
cytolytic
capacity.
Mechanistically,
LDRT
sensitizes
tumors
DPVB
recruiting
stem-like
Tpex,
progenitor
exhausted
cells,
draining
lymph
nodes
(dLNs)
into
tumor
via
CXCL10/CXCR3
axis.
Together,
these
results
further
support
rationale
combining
atezolizumab
bevacizumab,
its
clinical
translation.
