Molecular Pharmaceutics,
Год журнала:
2024,
Номер
22(1), С. 103 - 112
Опубликована: Ноя. 25, 2024
T
cells
are
indispensable
for
the
therapeutic
efficacy
of
cancer
immunotherapies,
including
immune
checkpoint
blockade.
However,
prolonged
antigen
exposure
also
drives
into
exhaustion,
which
is
characterized
by
upregulated
inhibitory
molecules,
impaired
effector
functions,
reduced
cytotoxicity,
altered
metabolism,
etc.
Noninvasive
monitoring
cell
exhaustion
allows
a
timely
identification
patients
that
most
likely
to
benefit
from
immunotherapies.
In
this
Review,
we
briefly
explain
biological
cascades
underlying
modulation
present
concise
update
on
nuclear
molecular
imaging
tracers
and
then
discuss
potential
opportunities
future
development.
CD8
+
tissue-resident
memory
T
lymphocytes
(TRM)
are
a
subset
of
tumor-infiltrating
(TILs)
that
mediate
innate
immunity.
Clinically,
they
can
prevent
tumor
development,
growth
and
metastasis
play
potential
role
in
immunosurveillance
long-term
immunity
head
neck
squamous
cell
carcinoma
(HNSCC).
This
systematic
review
meta-analysis
aimed
to
assess
the
prognostic
significance
TRM
cells,
identified
by
key
immunophenotypic
markers
CD103,
CD69,
CD49a
linked
patient
outcomes
such
as
overall
survival
(OS)
HNSCC
its
specified
subcategory,
OSCC.
PubMed,
Scopus,
Web
Science
databases
were
searched
systematically
include
original
research
articles
comprising
cross-sectional,
observational,
experimental
studies,
clinical
trials.
The
characteristics
studies
recorded
for
years
publication,
design,
cancer
types,
HPV
status,
staging,
diagnostic
assays,
markers,
immune
response
regulators.
Hazard
ratios
(HR)
with
confidence
intervals
(CI)
p-values
extracted
observing
association
between
and/or
exhibiting
cytotoxic
potential.
proportion
cells
co-expressing
was
estimated
extracting
actual
percentage
expression
TME
from
graphical
presentation
data
included
studies.
Among
276
11
reviewing
abstract
or
title
full-text
articles.
findings
these
demonstrated
strong
characterized
improved
OS
patients
HNSCC,
subtype,
Notably,
similar
trends
observed
within
relative
oropharyngeal
carcinomas
(OPSCC),
another
recognized
subtype
HNSCC.
pooled
HR
0.49
(95%
CI:
0.23–1.02,
p
<
0.001),
indicating
benefit
infiltration
related
subtypes
OSCC
OPSCC.
However,
at
aggregate
incidences
not
statistically
significant
(p
>
0.05).
Increased
expressing
is
associated
better
prognosis
registered
international
database
protocols
https://www.crd.york.ac.uk/prospero/
under
protocol
identifier:
CRD42024570177.
Clinical Reviews in Allergy & Immunology,
Год журнала:
2025,
Номер
68(1)
Опубликована: Апрель 2, 2025
Lymph
nodes
(LNs)
are
ovoid-shape
capsulated
structures
interposed
along
the
lymphatic
vessels.
Owing
to
their
unique
architecture,
LNs
place
immune
cell
types
in
distinct
compartments
allowing
effective
contact
of
antigens
them.
Their
efficient
function
results
concentration
and
bridging
antigen-presenting
cells
like
DCs
B
adaptive
immunity
(circulating
T
lymphocytes
remaining
monitor
antigens)
coordinate
responses.
In
a
healthy
LN,
primarily
clustered
lymphoid
follicles,
whereas
organized
deeper
paracortex
region.
Mast
(MCs)
among
cells;
normal
presence
or
pathologic
infiltration
has
been
reported
LNs.
MCs
enter
through
afferent
vessels
can
be
found
all
compartments,
ranging
from
subcapsular
sinus
deepest
sections
medullary
sinus;
however,
they
commonly
zone
but
rarely
follicles.
pathologies
with
LN
involvement
solid
tumors,
features
MC
accumulation
anatomical
region
within
differ
based
on
type
tumor
organ.
Moreover,
may
influence
trafficking
other
out
facilitate
migration
into
which
is
crucial
for
orchestrating
responses,
especially
vaccination;
moreover,
play
role
induction
peripheral
tolerance.
MC-released
mediators
including
TNF
tissue-resident
tryptase
LN-MCs
mediate
hyperplasia
extension
vasculature,
respectively.
support
lymphangiogenesis
by
releasing
VEGF-C
VEGF-D
vivo.
Further
research
anticipated
due
development
pharmaceuticals
that
impact
survival
inhibit
activation.
this
review,
we
summarize
current
literature
regarding
outcomes
focus
MC-mediated
responses
two
categories:
direct
cell-to-cell
mediator-based
interactions.
Molecular Immunology,
Год журнала:
2025,
Номер
182, С. 107 - 116
Опубликована: Апрель 19, 2025
CD4
T
cells
in
people
living
with
HIV
(PLWH)
on
antiretroviral
therapy
(ART)
often
exhibit
an
inflammaging
phenotype,
characterized
by
persistent
inflammation,
immune
activation,
exhaustion,
senescence,
and
apoptosis.
We
have
previously
demonstrated
that
inhibition
of
telomeric
repeat
factor
2
(TRF2)
protein
causes
accelerated
telomere
erosion
premature
cell
aging
PLWH.
In
this
study,
we
further
investigated
how
TRF2
is
inhibited
from
PLWH,
focusing
the
miRNA-mediated
mechanism.
found
miR-23a
significantly
increased,
whereas
repressed,
PLWH
compared
to
healthy
subjects
(HS).
Bioinformatics
analysis
revealed
3'UTR
a
potential
target
miR-23a.
Co-transfection
luciferase
construct
containing
into
HEK293T
suppresses
translation.
Notably,
receptor
(TCR)
activation
both
HS
increased
decreased
expression.
Furthermore,
increasing
led
decrease
level
increase
cellular
apoptosis
-
phenotype
similar
what
observed
Moreover,
knockdown
TRF2,
but
not
TRF1,
levels.
These
results
suggest
negatively
regulates
expression
cells;
thus,
targeting
may
level,
thereby
protect
integrity
restore
functions
ImmunoHorizons,
Год журнала:
2024,
Номер
8(9), С. 668 - 678
Опубликована: Сен. 1, 2024
Abstract
Systemic
lupus
erythematosus
is
an
autoimmune
disease
characterized
by
excessive
inflammation
and
production
of
pathogenic
Abs.
Histone
deacetylase
6
(HDAC6)
a
class
IIb
histone
deacetylase.
It
has
been
reported
that
selective
HDAC6
inhibition
decreases
in
mouse
models.
In
this
study,
sex-
age-matched
wild-type
(WT)
HDAC6−/−
mice
on
the
C57BL/6
background
were
administered
0.5
ml
pristane
or
PBS
i.p.
at
8–12
wk
age
euthanized
10
d
later.
At
sacrifice,
body
weight
spleen
measured,
sera
collected,
splenocytes
peritoneal
cells
harvested
for
flow
cytometry.
We
found
administration
increased
with
no
difference
between
WT
mice.
Pristane
promoted
population
CD11b+Ly6C++
inflammatory
monocytes
CD11b+Ly6G+
neutrophils.
Peritoneal
recruitment
these
neutrophils
was
significantly
decreased
compared
Flow
cytometry
results
showed
number
CD69+
T
B
also
induced
IFN
signature
genes
as
determined
RT-qPCR.
Furthermore,
not
affected
vitro
studies
J774A.1
revealed
inhibitor
(ACY-738)
acetylation
NF-κB
while
increasing
Stat1
phosphorylation,
which
resulted
inducible
NO
synthase
LPS/IFN-γ–stimulated
cells.
Taken
together,
demonstrate
although
may
inhibit
some
pathways,
others
remain
unaffected.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 27, 2024
Abstract
Background
Acute
myeloid
leukemia
(AML)
is
a
malignant
clonal
blood
disease
and
the
most
common
type
of
acute
in
adults.
Despite
continuous
advances
treatments,
long-term
prognosis
AML
has
not
improved
substantially.
Tissue-resident
memory
T
cells
(TRMs)
infiltrating
solid
tumors
could
influence
tumor
progression
response
to
immune
therapies;
however,
proportion
prognostic
significance
TRMs
bone
marrow
(BM)
patients
with
are
unclear.
Methods
We
use
flow
cytometry
assay
phenotypic
49
BM
samples
from
newly
diagnosed
(ND-AML).
The
Kaplan–Meier
Plotter
database
verified
relationship
between
expression
CD8
+
TRM-like
cell
characteristic
genes
(CD8A,
CD69,
TOX)
patient
survival.
Additionally,
further
explored
existence
function
by
analyzing
single
proteo-genomic
dataset
healthy.
Results
found
that
effector
(TEM)
highly
expressed
CD69
(CD8
cells),
their
number
significantly
increased
ND-AML
compared
HIs.
high
subset
associated
poor
overall
survival
rate
was
reduced,
especially
M4
M5
subtypes.
Phenotypic
analysis
revealed
subpopulation
exhibited
exhausted
characteristics,
but
its
CD27
CD28
low
CD57
suggest
proliferative
potential.
single-cell
proteogenomic
confirmed
checkpoints
costimulatory
molecules.
Conclusions
accumulation
be
considered
as
an
related
prediction
marker
for
AML.
Although
mechanisms
driving
escape
remains
unknown,
we
believe
targeted
reversal
this
through
checkpoint
inhibitors
another
immune-related
“brake”
may
benefit
some
Blood Science,
Год журнала:
2024,
Номер
6(3), С. e00194 - e00194
Опубликована: Июнь 6, 2024
Tissue-resident
memory
T
(TRM)
cells
infiltrating
solid
tumors
could
influence
tumor
progression
and
the
response
to
immune
therapies.
However,
proportion
prognostic
value
of
TRM
in
bone
marrow
(BM)
patients
with
acute
myeloid
leukemia
(AML)
are
unclear.
In
this
study,
we
used
flow
cytometry
assay
phenotype
49
BM
samples
from
newly
diagnosed
AML
(ND-AML).
We
found
that
CD8
+
effector
(TEM)
highly
expressed
CD69
(CD8
TRM-like
cells),
their
percentage
was
significantly
increased
ND-AML
compared
healthy
individuals
(HI).
The
high
subset
associated
poor
overall
survival
our
cohort.
Kaplan–Meier
Plotter
database
verified
a
reduced
rate
among
expression
cell
characteristic
genes
(
CD8A
,
TOX
),
especially
M4
M5
subtypes.
Phenotypic
analysis
revealed
subpopulation
exhibited
exhausted
characteristics,
but
its
CD27
CD28
low
CD57
suggested
proliferative
potential.
single-cell
proteogenomic
dataset
confirmed
existence
checkpoints
costimulatory
molecules.
conclusion,
accumulation
be
an
immune-related
prediction
marker
for
AML.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 12, 2024
Abstract
The
field
of
synthetic
biology
has
expanded
the
possibilities
for
controlling
cellular
functions,
particularly
in
development
mammalian
cells
therapeutic
applications.
This
study
explored
application
magnetogenetic
tools
to
regulate
T
cell
activity,
a
crucial
aspect
developing
advanced
immunotherapies.
Magnetogenetic
use
magnetic
fields
remotely
control
engineered
ion
channels
and
protein
domains,
providing
non-invasive,
deep-tissue
stimulation
that
overcomes
limitations
traditional
methods.
We
investigated
effects
three
-
TRPV1
(TRP1-Fer)
TRPV4
(TRP4-Fer)
channels,
Electromagnetic
Perceptive
Gene
(EPG)
Jurkat
cells.
First,
calcium
concentration
measurements
confirmed
activity
these
within
Using
qPCR
proteomics
analysis,
we
then
analyzed
their
impact
on
activation,
signaling,
mitochondrial
function,
membrane
integrity,
gene
expression
under
both
stimulated
(with
antigens)
non-stimulated
conditions.
Our
results
revealed
significant
upregulation
activation
calcium-handling
proteins
cells,
indicating
enhanced
cytoskeletal
dynamics
compared
controls.
However,
unexpectedly
led
deactivation
investigation
showed
while
induction
alone
deactivated
antigen
conjunction
with
amplified
activation.
highlights
potential
magnetogenetics
precisely
modulate
presenting
promising
avenues
more
effective
controlled
findings
also
underscore
need
careful
optimization
mitigate
adverse
integrity
function.