Cancer Research,
Journal Year:
2025,
Volume and Issue:
85(8), P. 1424 - 1440
Published: March 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.
Abstract
T
cell
is
an
indispensable
component
of
the
immune
system
and
its
multifaceted
functions
are
shaped
by
distinct
types
their
various
states.
Although
multiple
computational
models
exist
for
predicting
abundance
diverse
types,
tools
assessing
states
to
characterize
degree
resting,
activation,
suppression
lacking.
To
address
this
gap,
a
robust
nuanced
scoring
tool
called
state
identifier
(TCellSI)
leveraging
Mann–Whitney
U
statistics
established.
The
TCellSI
methodology
enables
evaluation
eight
states—Quiescence,
Regulating,
Proliferation,
Helper,
Cytotoxicity,
Progenitor
exhaustion,
Terminal
Senescence—from
transcriptome
data,
providing
scores
(TCSS)
samples
through
specific
marker
gene
sets
compiled
reference
spectrum.
Validated
against
sizeable
pseudo‐bulk
actual
bulk
RNA‐seq
data
across
range
not
only
accurately
characterizes
but
also
surpasses
existing
well‐discovered
signatures
in
reflecting
nature
cells.
Significantly,
demonstrates
predictive
value
environment,
correlating
with
patient
prognosis
responses
immunotherapy.
For
better
utilization,
readily
accessible
user‐friendly
R
package
web
server
(
https://guolab.wchscu.cn/TCellSI/
).
By
offering
insights
into
personalized
cancer
therapies,
has
potential
improve
treatment
outcomes
efficacy.
Theranostics,
Journal Year:
2024,
Volume and Issue:
14(9), P. 3526 - 3547
Published: Jan. 1, 2024
Immunotherapy
has
demonstrated
its
potential
to
improve
the
prognosis
of
patients
with
hepatocellular
carcinoma
(HCC);
however,
patients'
responses
immunotherapy
vary
a
lot.
A
comparative
analysis
tumor
microenvironment
(TME)
in
responders
and
non-responders
is
expected
unveil
mechanisms
responsible
for
resistance
provide
treatment
targets.
MedComm,
Journal Year:
2025,
Volume and Issue:
6(1)
Published: Jan. 1, 2025
Abstract
Tissue‐resident
memory
T
(T
RM
)
cells
are
crucial
components
of
the
immune
system
that
provide
rapid,
localized
responses
to
recurrent
pathogens
at
mucosal
and
epithelial
barriers.
Unlike
circulating
cells,
located
within
peripheral
tissues,
they
play
vital
roles
in
antiviral,
antibacterial,
antitumor
immunity.
Their
unique
retention
activation
mechanisms,
including
interactions
with
local
expression
adhesion
molecules,
enable
their
persistence
immediate
functionality
diverse
tissues.
Recent
advances
have
revealed
important
chronic
inflammation,
autoimmunity,
cancer,
illuminating
both
protective
pathogenic
potential.
This
review
synthesizes
current
knowledge
on
cells’
molecular
signatures,
maintenance
pathways,
functional
dynamics
across
different
We
also
explore
other
such
as
B
macrophages,
dendritic
highlighting
complex
network
underpins
efficacy
surveillance
response.
Understanding
nuanced
regulation
is
essential
for
developing
targeted
therapeutic
strategies,
vaccines
immunotherapies,
enhance
while
mitigating
adverse
effects.
Insights
into
biology
hold
promise
innovative
treatments
infectious
diseases,
autoimmune
conditions.
Deleted Journal,
Journal Year:
2025,
Volume and Issue:
33(1), P. 200933 - 200933
Published: Jan. 14, 2025
Metabolic
features
are
crucial
in
tumor
immune
interactions,
but
their
relationship
with
antitumor
responses
is
not
yet
fully
understood.
This
study
used
Mendelian
randomization
analysis
to
identify
the
causal
relationships
between
blood
metabolites
and
cells
evaluate
effects
of
metabolic
pathways
reactions
on
various
cancers.
Levels
156
exhibited
significant
associations
selected
cells.
enrichment
indicated
laurate,
propionyl-carnitine,
carnitine
l-acetylcarnitine
enriched
fatty
acid
(FA)
metabolism
pathways.
These
significantly
correlated
CD8+
T
cell
function
signatures
environment
favor
better
prognostic
outcomes.
contributing
immunotherapy
were
identified
establish
immuno-metabolic
reaction
score
(IMRS).
IMRS
infiltration
levels
signature
scores
either
10×
Visium
spatial
transcriptomic
or
RNA-seq
samples.
Finally,
could
predict
favorable
survival
outcomes
different
cancer
patients
treated
immunotherapy.
Our
revealed
a
link
certain
related
landscape
functions.
results
promote
accurate
stratification
before
treatment
improve
efficacy
Signal Transduction and Targeted Therapy,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: Jan. 16, 2025
Tissue-resident
immune
cells
(TRICs)
are
a
highly
heterogeneous
and
plastic
subpopulation
of
that
reside
in
lymphoid
or
peripheral
tissues
without
recirculation.
These
endowed
with
notably
distinct
capabilities,
setting
them
apart
from
their
circulating
leukocyte
counterparts.
Many
studies
demonstrate
complex
roles
both
health
disease,
involving
the
regulation
homeostasis,
protection,
destruction.
The
advancement
tissue-resolution
technologies,
such
as
single-cell
sequencing
spatiotemporal
omics,
provides
deeper
insights
into
cell
morphology,
characteristic
markers,
dynamic
transcriptional
profiles
TRICs.
Currently,
reported
TRIC
population
includes
tissue-resident
T
cells,
memory
B
(BRM)
innate
lymphocytes,
macrophages,
neutrophils
(TRNs),
mast
but
unignorably
existence
TRNs
is
controversial.
Previous
focus
on
one
specific
diseases,
however,
origins,
developmental
trajectories,
intercellular
cross-talks
every
type
not
fully
summarized.
In
addition,
systemic
overview
TRICs
disease
progression
development
parallel
therapeutic
strategies
lacking.
Here,
we
describe
function
characteristics
all
types
major
diseases.
We
shed
light
how
to
harness
offer
new
targets
present
burning
questions
this
field.
The Journal of Experimental Medicine,
Journal Year:
2025,
Volume and Issue:
222(2)
Published: Jan. 22, 2025
Tissue-resident
memory
T
cells
(TRM)
provide
frontline
protection
against
pathogens
and
emerging
malignancies.
Tumor-infiltrating
lymphocytes
(TIL)
with
TRM
features
are
associated
improved
clinical
outcomes.
However,
the
cellular
interactions
that
program
differentiation
function
not
well
understood.
Using
murine
genetic
models
targeted
spatial
transcriptomics,
we
found
CD8+
cell–derived
chemokine
XCL1
is
critical
for
formation
conventional
DC1
(cDC1)
supported
positioning
of
intestinal
during
acute
viral
infection.
In
tumors,
enforced
Xcl1
expression
by
antigen-specific
promoted
intratumoral
cDC1
accumulation
cell
persistence,
leading
to
overall
survival.
Notably,
analysis
human
TIL
revealed
conserved
XCL2.
Thus,
have
shown
XCL1–XCR1
axis
plays
a
non-cell
autonomous
role
in
guiding
tumor
control.
