Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: May 15, 2025
During
chronic
infection
and
tumor
progression,
CD8+
T
cells
lose
their
effector
functions
become
exhausted.
These
exhausted
are
heterogeneous
comprised
of
progenitors
that
give
rise
to
effector-like
or
terminally-exhausted
cells.
The
precise
cues
mechanisms
directing
subset
formation
incompletely
understood.
Here,
we
show
growth
factor
independent-1
(Gfi1)
is
dynamically
regulated
in
LCMV
Clone
13
infection,
a
previously
under-described
Ly108+CX3CR1+
expresses
low
levels
Gfi1
while
other
established
subsets
have
high
expression.
possess
distinct
chromatin
profiles
represent
transitory
develops
cells,
process
dependent
on
Gfi1.
Similarly,
tumor-infiltrating
required
for
the
terminally
differentiated
endogenous
as
well
anti-CTLA-induced
anti-tumor
responses.
Taken
together,
key
regulator
Science Immunology,
Journal Year:
2025,
Volume and Issue:
10(105)
Published: March 7, 2025
Although
checkpoint
blockade
temporarily
improves
exhausted
CD8
T
(Tex)
cell
function,
the
underlying
Tex
epigenetic
landscape
remains
largely
unchanged,
preventing
durable
"reinvigoration"
in
cancer
and
chronic
infections.
The
transcription
factor
TOX
initiates
programming,
yet
it
unclear
whether
continually
preserves
biology
after
establishment.
Here,
we
demonstrated
that
induced
ablation
committed
cells
resulted
apoptotic-driven
loss
of
cells,
reduced
expression
inhibitory
receptors,
decreased
terminal
differentiation.
Gene
profiling
revealed
a
critical
role
for
maintaining
chromatin
accessibility
transcriptional
patterns
cells.
Moreover,
removal
endows
established
with
greater
fate
flexibility
to
differentiate
into
more
functional
effector-like
Thus,
continuous
acts
as
barrier
reinforcing
developmental
fate.
manipulation
even
establishment
could
therefore
provide
therapeutic
opportunities
rewire
infections
or
cancer.
Cancer Cell,
Journal Year:
2024,
Volume and Issue:
42(4), P. 623 - 645.e10
Published: March 14, 2024
Genes
limiting
T
cell
antitumor
activity
may
serve
as
therapeutic
targets.
It
has
not
been
systematically
studied
whether
there
are
regulators
that
uniquely
or
broadly
contribute
to
fitness.
We
perform
genome-scale
CRISPR-Cas9
knockout
screens
in
primary
CD8
cells
uncover
genes
negatively
impacting
fitness
upon
three
modes
of
stimulation:
(1)
intense,
triggering
activation-induced
death
(AICD);
(2)
acute,
expansion;
(3)
chronic,
causing
dysfunction.
Besides
established
regulators,
we
controlling
either
specifically
commonly
differential
stimulation.
Dap5
ablation,
ranking
highly
all
screens,
increases
translation
while
enhancing
tumor
killing.
Loss
Icam1-mediated
homotypic
clustering
amplifies
expansion
and
effector
functions
after
both
acute
intense
Lastly,
Ctbp1
inactivation
induces
functional
persistence
exclusively
chronic
Our
results
functionally
annotate
based
on
their
unique
shared
contribution
traits
activity.
Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(7), P. 114458 - 114458
Published: July 1, 2024
Regulatory
T
(Treg)
cells
play
a
critical
regulatory
role
in
the
immune
system
by
suppressing
excessive
responses
and
maintaining
balance.
The
effective
migration
of
Treg
is
crucial
for
controlling
development
progression
inflammatory
diseases.
However,
mechanisms
responsible
directing
into
tissue
remain
incompletely
elucidated.
In
this
study,
we
identified
BAF60b,
subunit
switch/sucrose
nonfermentable
(SWI/SNF)
chromatin
remodeling
complexes,
as
positive
regulator
cell
that
inhibits
inflammation
experimental
autoimmune
encephalomyelitis
(EAE)
colitis
animal
models.
Mechanistically,
transcriptome
genome-wide
chromatin-landscaped
analyses
demonstrated
BAF60b
interacts
with
transcription
factor
RUNX1
to
promote
expression
CCR9
on
cells,
which
turn
affects
their
ability
migrate
tissues.
Our
work
provides
insights
essential
regulating
its
impact
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Nov. 5, 2024
RNA
methylation
is
an
important
regulatory
process
to
determine
immune
cell
function
but
how
it
affects
the
anti-tumor
activity
of
CD8
T
cells
not
fully
understood.
Here
we
show
that
N6-methyladenosine
(m6A)
reader
YTHDF2
highly
expressed
in
early
effector
or
effector-like
cells.
We
find
facilitates
nascent
synthesis,
and
m6A
recognition
fundamental
for
this
distinctively
nuclear
protein,
which
also
reinforces
its
autoregulation
at
level.
Loss
exacerbates
tumor
progression
confers
unresponsiveness
PD-1
blockade
mice
humans.
In
addition
initiating
decay
necessary
mitochondrial
fitness,
orchestrates
chromatin
changes
promote
polyfunctionality.
interacts
with
IKZF1/3,
sustained
transcription
their
target
genes.
Accordingly,
immunotherapy-induced
efficacy
could
be
largely
restored
YTHDF2-deficient
through
combinational
use
IKZF1/3
inhibitor
lenalidomide
a
mouse
model.
Thus,
coordinates
epi-transcriptional
transcriptional
networks
potentiate
immunity,
inform
therapeutic
intervention.
has
recently
identified
as
mechanism
governing
functional
cellular
states,
effect
on
antitumour
+
explored.
authors
assign
essential
nuclear,
m6A-recognition-dependent
YTHDF2,
which,
conjunction
role
IKZF1/3-mediated
gene
transcription,
governs
Epigenetics & Chromatin,
Journal Year:
2025,
Volume and Issue:
18(1)
Published: April 23, 2025
The
SWI/SNF
complex
was
first
identified
in
yeast
and
named
after
studies
of
mutants
critical
for
the
mating-type
switch
(SWI)
sucrose
non-fermenting
(SNF)
pathways.The
plays
a
pivotal
role
regulating
gene
expression
by
altering
chromatin
structure
to
promote
or
suppress
specific
genes,
maintain
stem
cell
pluripotency,
participate
various
biological
processes.
Mutations
are
highly
prevalent
human
cancers,
significantly
impacting
tumor
suppressive
oncogenic
functions
influencing
initiation
progression.
This
review
focuses
on
mechanisms
which
ARID1A/ARID1B,
PBRM1,
SMARCB1,
SMARCA2/SMARCA4
contribute
cancer,
immunoregulatory
roles
complex,
its
involvement
DNA
repair
pathways,
synthetic
lethality,
applications
precision
oncology.
