Cancer Research,
Год журнала:
2025,
Номер
85(8), С. 1424 - 1440
Опубликована: Март 5, 2025
PD-1
pathway
inhibitors
have
revolutionized
cancer
therapy.
However,
most
patients
do
not
durably
benefit,
highlighting
the
need
for
biomarkers
to
stratify
as
responders
or
nonresponders.
Although
CD8+
tumor-infiltrating
lymphocytes
(TIL)
been
associated
with
immune
checkpoint
therapy
response,
there
is
no
consensus
on
which
TIL
subpopulations
prognostic
value.
Preclinical
studies
focused
progenitor-like
exhausted
T
cells
(TPEX)
because
TPEX
proliferate
more
in
response
than
other
T-cell
(TEX)
subpopulations.
inhibitor
treatment
drives
differentiation
into
TEX
populations
that
can
mediate
antitumor
immunity.
These
data
complicate
ability
identify
prognostically
important
predict
response.
In
this
study,
we
found
advanced
melanoma
≥20%
of
TILs
coexpressing
and
CTLA4
(termed
CPHi
TIL)
had
better
objective
rates
survival
following
monotherapy
those
below
threshold.
Characterization
subset
using
bulk
single-cell
RNA
sequencing
showed
although
TPEX-like
were
present
within
subset,
they
minority
these
cells.
Rather,
population
was
numerically
dominated
by
subsets,
including
cycling,
terminally
exhausted-like,
cytotoxic-like,
and/or
resident
memory-like
populations,
a
enriched
glycolytic
genes.
Collectively,
show
correlate
melanoma,
but
heterogeneous
mix
different
may
differentially
contribute
immunity
blockade.
Significance:
The
PD-1+
CTLA4+
lymphocyte
correlating
immunotherapy
subpopulations,
has
implications
optimizing
checkpoint-based
immunotherapy.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 15, 2025
A
diverse
naive
CD8
T
cell
repertoire
is
essential
to
provide
broad
protection
against
infection
and
cancer.
Aging
diminishes
cells,
reducing
potential
diversity
leading
lymph
node
contraction.
Here,
we
revealed
that
this
decline
occurs
earlier
in
males,
resulting
significant
sex
differences
immunity
during
middle
age.
Earlier
life,
cells
males
become
virtual
memory
prone
premature
senescence.
Due
androgen-driven
thymic
atrophy
naïve
are
insufficiently
replenished.
Therapeutic
thymus
rejuvenation
via
testosterone
ablation
restored
nodes
of
middle-aged
male
mice,
enhanced
tumor
recognition.
These
findings
show
the
crucial
role
age
on
repertoires
suggest
strategies
restore
immune
function
aging.
Advanced Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 17, 2025
Strategically
targeting
lymph
nodes
(LNs)
to
orchestrate
the
initiation
and
regulation
of
adaptive
immune
responses
is
one
most
pressing
challenges
in
context
vaccination.
Herein,
a
series
polymer-TLR
agonist
conjugates
(PTACs)
developed
investigate
impact
dendritic-topological
characteristics
on
their
LN
activity
vivo,
molecular
weight
(MW)
pharmacokinetics
support
homing.
Notably,
dendritic
6-arm
PTAC
with
MW
60
kDa
(6A-PTAC-60k)
rapidly
delivered
cargo
draining
LNs
after
administration
peripheral
tissues.
Specifically,
this
topologic
structure
ameliorated
behavior
within
lymphatic
vessels
LNs,
including
an
elevated
amount
TLR7/8
improved
distribution
pattern
among
barrier
cells
cells,
increased
permeability,
prolonged
retention.
Furthermore,
6A-PTAC-60k
formulation
induced
broad
antibody
T
cell
responses,
enhancing
vaccine
immunogenicity
suppressing
tumor
growth.
The
results
revealed
that
both
topology
polymers
are
crucial
factors
for
immunoadjuvant
functional
which,
turn,
enhanced
formulation.
This
study
may
provide
chemical
structural
basis
optimizing
design
delivery
systems.
Cancer Research,
Год журнала:
2025,
Номер
85(8), С. 1424 - 1440
Опубликована: Март 5, 2025
PD-1
pathway
inhibitors
have
revolutionized
cancer
therapy.
However,
most
patients
do
not
durably
benefit,
highlighting
the
need
for
biomarkers
to
stratify
as
responders
or
nonresponders.
Although
CD8+
tumor-infiltrating
lymphocytes
(TIL)
been
associated
with
immune
checkpoint
therapy
response,
there
is
no
consensus
on
which
TIL
subpopulations
prognostic
value.
Preclinical
studies
focused
progenitor-like
exhausted
T
cells
(TPEX)
because
TPEX
proliferate
more
in
response
than
other
T-cell
(TEX)
subpopulations.
inhibitor
treatment
drives
differentiation
into
TEX
populations
that
can
mediate
antitumor
immunity.
These
data
complicate
ability
identify
prognostically
important
predict
response.
In
this
study,
we
found
advanced
melanoma
≥20%
of
TILs
coexpressing
and
CTLA4
(termed
CPHi
TIL)
had
better
objective
rates
survival
following
monotherapy
those
below
threshold.
Characterization
subset
using
bulk
single-cell
RNA
sequencing
showed
although
TPEX-like
were
present
within
subset,
they
minority
these
cells.
Rather,
population
was
numerically
dominated
by
subsets,
including
cycling,
terminally
exhausted-like,
cytotoxic-like,
and/or
resident
memory-like
populations,
a
enriched
glycolytic
genes.
Collectively,
show
correlate
melanoma,
but
heterogeneous
mix
different
may
differentially
contribute
immunity
blockade.
Significance:
The
PD-1+
CTLA4+
lymphocyte
correlating
immunotherapy
subpopulations,
has
implications
optimizing
checkpoint-based
immunotherapy.
