While
immune-checkpoint
blockade
(ICB)
has
revolutionized
treatment
of
metastatic
melanoma
over
the
last
decade,
identification
broadly
applicable
robust
biomarkers
been
challenging,
driven
in
large
part
by
heterogeneity
ICB
regimens
and
patient
tumor
characteristics.
To
disentangle
these
features,
we
performed
a
standardized
meta-analysis
eight
cohorts
patients
treated
with
anti-PD-1
(n=290),
anti-CTLA-4
(n=175),
combination
anti-PD-1/anti-CTLA-4
(n=51)
RNA
sequencing
pre-treatment
clinical
annotations.
Stratifying
immune-high
vs
-low
tumors,
found
that
surprisingly,
high
immune
infiltrate
was
biomarker
for
response
to
ICB,
but
not
alone.
Additionally,
hypoxia-related
signatures
were
associated
non-response
anti-PD-1,
only
amongst
infiltrate-high
melanomas.
In
cohort
scRNA-seq
melanoma,
hypoxia
also
correlated
immunosuppression
changes
tumor-stromal
communication
microenvironment
(TME).
Clinically
actionable
targets
signaling
uniquely
expressed
across
different
cell
types.
We
focused
on
one
such
target,
HIF-2
Seminars in Immunology,
Journal Year:
2024,
Volume and Issue:
74-75, P. 101900 - 101900
Published: July 1, 2024
Dendritic
cells
(DCs)
are
crucial
for
initiating
immune
responses
against
tumours
by
presenting
antigens
to
T
cells.
Glycosylation,
particularly
sialylation,
plays
a
significant
role
in
regulating
cell
functions,
modulating
protein
folding
and
signalling.
This
review
aimed
provide
comprehensive
overview
of
how
sialic
acids
influence
key
aspects
DC
biology,
including
maturation,
migration,
antigen
presentation,
interactions.
Sialic
endocytosis,
affecting
their
ability
uptake
present
antigens,
while
guiding
migration
lymph
nodes
inflamed
tissues.
Removing
enhances
DC-mediated
presentation
cells,
potentially
boosting
responses.
Additionally,
sialylated
glycans
on
DCs
modulate
checkpoints,
which
can
impact
tumour
immunity.
Hypersialylation
mucins
further
promotes
evasion
interacting
with
DCs.
Understanding
the
interplay
between
sialylation
functions
offers
promising
avenues
enhancing
cancer
immunotherapy.
While
immune-checkpoint
blockade
(ICB)
has
revolutionized
treatment
of
metastatic
melanoma
over
the
last
decade,
identification
broadly
applicable
robust
biomarkers
been
challenging,
driven
in
large
part
by
heterogeneity
ICB
regimens
and
patient
tumor
characteristics.
To
disentangle
these
features,
we
performed
a
standardized
meta-analysis
eight
cohorts
patients
treated
with
anti-PD-1
(n=290),
anti-CTLA-4
(n=175),
combination
anti-PD-1/anti-CTLA-4
(n=51)
RNA
sequencing
pre-treatment
clinical
annotations.
Stratifying
immune-high
vs
-low
tumors,
found
that
surprisingly,
high
immune
infiltrate
was
biomarker
for
response
to
ICB,
but
not
alone.
Additionally,
hypoxia-related
signatures
were
associated
non-response
anti-PD-1,
only
amongst
infiltrate-high
melanomas.
In
cohort
scRNA-seq
melanoma,
hypoxia
also
correlated
immunosuppression
changes
tumor-stromal
communication
microenvironment
(TME).
Clinically
actionable
targets
signaling
uniquely
expressed
across
different
cell
types.
We
focused
on
one
such
target,
HIF-2
