For
decades,
the
3
therapeutic
pillars
for
head
and
neck
squamous
cell
carcinoma
(HNSCC)
have
been
radiation
therapy,
chemotherapy,
surgery.
In
recent
years,
a
fourth
pillar,
immunotherapy,
has
shifted
existing
paradigm
of
oncologic
care
by
improving
survival
outcomes.
This
narrative
review
highlights
key
completed
ongoing
clinical
trials
that
led
to
new
approaches
are
aiming
further
alter
current
standard
care.
Immunotherapy
in
HNSCC
first
saw
success
phase
with
immune
checkpoint
inhibitors
(ICIs)
programmed
death
1
protein
patients
recurrent
or
metastatic
(R/M)
disease.
However,
only
approximately
15%
20%
R/M
achieve
durable
responses.
Subsequent
aimed
broaden
ICIs
definitive
curative
setting,
combination
established
chemoradiation
modalities.
These
studies
yielded
disappointing
results,
raising
concerns
concurrent
administration
ICI
chemoradiation-
radiation-induced
attenuation
responses
may
contribute
lack
efficacy.
Therefore,
attempted
introduce
sequentially,
either
prior
surgery
neoadjuvant
setting
following
treatment
adjuvant
maintenance
setting.
demonstrated
mixed
results
but
promising
initial
from
early
demonstrating
signals
response.
Further
currently
underway
various
combinatorial
settings
assess
response
rates
survival.
The
introduction
brought
dramatic
shift
landscape
HNSCC.
Completed
provided
hope
patients,
failures
several
suggest
based
on
biologic
understanding
required
expand
immunotherapeutic
approaches.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2025,
Volume and Issue:
44(1)
Published: Feb. 18, 2025
Abstract
Background
Co-targeting
of
immune
checkpoint
inhibitors
(ICI)
CTLA-4
and
PD-1
has
recently
become
the
new
first-line
standard
care
therapy
pleural
mesothelioma
(PM)
patients,
with
a
significant
improvement
overall
survival
(OS)
over
conventional
chemotherapy.
The
analysis
by
tumor
histotype
demonstrated
greater
efficacy
ICI
compared
to
chemotherapy
in
non-epithelioid
(non-E)
vs.
epithelioid
(E)
PM,
although
some
E
PM
patients
also
benefit
from
treatment.
This
evidence
suggests
that
molecular
features,
beyond
histotype,
could
be
relevant
improve
PM.
Among
these,
DNA
methylation
emerges
as
promising
factor
explore,
due
its
potential
role
driving
phenotype
cancer
cells.
Therefore,
we
utilized
panel
cultured
cells
different
provide
preclinical
supporting
landscape,
along
pharmacologic
modulation,
prospectively
patients.
Methods
methylome
profile
(EPIC
array)
distinct
(
n
=
5)
non-E
9)
cell
lines
was
analyzed,
followed
integrated
their
associated
transcriptomic
(Clariom
S
array),
before
after
vitro
treatment
hypomethylating
agent
(DHA)
guadecitabine.
most
variable
methylated
probes
were
selected
calculate
score
(CIMP
index)
for
each
line
at
baseline.
Genes
differentially
expressed
(DE)
(DM)
then
gene
ontology
analysis.
Results
CIMP
index
stratified
into
two
classes,
(hyper-methylated;
7)
LOW
(hypo-methylated;
7),
regardless
or
histotype.
Integrated
transcriptome
analyses
revealed
exhibited
substantial
number
hyper-methylated,
silenced
genes,
which
negatively
impacted
Treatment
DHA
reverted
methylation-driven
immune-compromised
enhanced
constitutive
immune-favorable
Conclusion
study
highlighted
relevance
shaping
classification
cells,
independent
histological
subtypes.
identified
shifting
towards
an
state
highlights
evaluation
phase
I/II
clinical
trials
investigating
epigenetic-based
combinations
reverse
resistance
mechanisms.
Metabolites,
Journal Year:
2025,
Volume and Issue:
15(3), P. 144 - 144
Published: Feb. 21, 2025
Amino
acids
are
crucial
components
of
proteins,
key
molecules
in
cellular
physiology
and
homeostasis.
However,
they
also
involved
a
variety
other
mechanisms,
such
as
energy
homeostasis,
nitrogen
exchange,
further
synthesis
bioactive
compounds,
production
nucleotides,
or
activation
signaling
pathways.
Moreover,
amino
their
metabolites
have
immunoregulatory
properties,
significantly
affecting
the
behavior
immune
cells.
Immunotherapy
is
one
oncological
treatment
methods
that
improves
cytotoxic
properties
one’s
own
system.
Thus,
enzymes
catalyzing
acid
metabolism,
together
with
themselves,
can
affect
antitumor
responses
to
immunotherapy.
In
this
review,
we
will
discuss
involvement
tryptophan,
glutamine,
asparagine
metabolism
cells
targeted
by
immunotherapy
summarize
results
most
recent
investigations
on
impact
For
decades,
the
3
therapeutic
pillars
for
head
and
neck
squamous
cell
carcinoma
(HNSCC)
have
been
radiation
therapy,
chemotherapy,
surgery.
In
recent
years,
a
fourth
pillar,
immunotherapy,
has
shifted
existing
paradigm
of
oncologic
care
by
improving
survival
outcomes.
This
narrative
review
highlights
key
completed
ongoing
clinical
trials
that
led
to
new
approaches
are
aiming
further
alter
current
standard
care.
Immunotherapy
in
HNSCC
first
saw
success
phase
with
immune
checkpoint
inhibitors
(ICIs)
programmed
death
1
protein
patients
recurrent
or
metastatic
(R/M)
disease.
However,
only
approximately
15%
20%
R/M
achieve
durable
responses.
Subsequent
aimed
broaden
ICIs
definitive
curative
setting,
combination
established
chemoradiation
modalities.
These
studies
yielded
disappointing
results,
raising
concerns
concurrent
administration
ICI
chemoradiation-
radiation-induced
attenuation
responses
may
contribute
lack
efficacy.
Therefore,
attempted
introduce
sequentially,
either
prior
surgery
neoadjuvant
setting
following
treatment
adjuvant
maintenance
setting.
demonstrated
mixed
results
but
promising
initial
from
early
demonstrating
signals
response.
Further
currently
underway
various
combinatorial
settings
assess
response
rates
survival.
The
introduction
brought
dramatic
shift
landscape
HNSCC.
Completed
provided
hope
patients,
failures
several
suggest
based
on
biologic
understanding
required
expand
immunotherapeutic
approaches.
