Frontiers in Cardiovascular Medicine,
Год журнала:
2024,
Номер
11
Опубликована: Окт. 24, 2024
Immune
checkpoint
inhibitor-associated
myocarditis
(ICI
myocarditis)
is
an
infrequent
but
potentially
fatal
immune-related
adverse
event.
This
study
aimed
to
identify
valuable
indicators
for
risk
prediction
and
evaluation
of
disease
severity
outcomes.
Basic Research in Cardiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 17, 2024
Abstract
Immune
checkpoint
inhibitors
(ICIs)
have
revolutionized
cancer
therapy
by
unleashing
the
power
of
immune
system
against
malignant
cells.
However,
their
use
is
associated
with
a
spectrum
adverse
effects,
including
cardiovascular
complications,
which
can
pose
significant
clinical
challenges.
Several
mechanisms
contribute
to
toxicity
ICIs.
First,
dysregulation
checkpoints,
such
as
cytotoxic
T-lymphocyte-associated
protein
4
(CTLA-4)
and
programmed
cell
death
protein-1
(PD-1)
its
ligand
(PD-L1),
molecular
mimicry
cardiac
autoantigens,
leads
immune-related
events,
myocarditis
vasculitis.
These
events
result
from
aberrant
activation
T
cells
self-antigens
within
myocardium
or
vascular
endothelium.
Second,
disruption
homeostasis
ICIs
lead
autoimmune-mediated
inflammation
tissues,
manifesting
dysfunction
heart
failure,
arrhythmias,
pericarditis.
Furthermore,
upregulation
inflammatory
cytokines,
particularly
tumor
necrosis
factor-alpha,
interferon-γ,
interleukin-1β,
interleukin-6,
interleukin-17
contributes
endothelial
dysfunction,
plaque
destabilization,
thrombosis,
exacerbating
risk
on
long
term.
Understanding
intricate
side
effects
induced
crucial
for
optimizing
patient
care
ensure
safe
effective
integration
immunotherapy
into
broader
range
treatment
protocols.
The
implications
these
underscore
importance
vigilant
monitoring
early
detection
in
patients
receiving
Future
key
pathological
mediators
biomarkers
may
aid
prompt
diagnosis
cardiotoxicity
will
allow
timely
interventions.
Journal of Clinical Immunology,
Год журнала:
2024,
Номер
44(3)
Опубликована: Март 15, 2024
Myocarditis
can
be
caused
by
viral
infection,
drug
reaction
or
general
inflammatory
condition.
To
provide
understanding
on
myocarditis,
we
describe
clinical,
genetic,
and
immunological
properties
of
a
young
male
patient
who
suffered
from
recurrent
myocarditis
episodes
since
the
age
four
years.
Electrocardiography,
troponin
I/T,
echocardiography,
myocardial
magnetic
resonance
imaging
histological
findings
were
consistent
with
episodes.
Homozygous
c.245
A
>
G
p.Tyr82Cys
pathogenic
variant
in
Hepatitis
Virus
Cellular
Receptor
2
(HAVCR2)
gene
encoding
T
cell
immunoglobulin
mucin
domain-containing
protein
3
(TIM-3)
receptor
was
found.
Peripheral
blood
mononuclear
cells
collected
when
asymptomatic;
CD4
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 28, 2025
The
advent
of
immune
checkpoint
inhibitors
(ICIs)
has
revolutionized
cancer
treatment,
offering
life-saving
benefits
to
tumor
patients.
However,
the
utilize
ICI
agents
is
often
accompanied
by
immune-related
adverse
events
(irAEs),
among
which
cardiovascular
toxicities
have
attracted
more
and
attention.
induced
predominantly
present
as
acute
myocarditis
chronic
atherosclerosis,
both
are
driven
excessive
activation.
Reprogramming
T
cells
macrophages
been
demonstrated
a
pivotal
factor
in
pathogenesis
these
complications.
Therapeutic
strategies
targeting
glycolysis,
fatty
acid
oxidation,
reactive
oxygen
species
(ROS)
production
some
other
key
signaling
shown
promise
mitigating
hyperactivation
inflammation.
In
this
review,
we
explored
intricate
mechanisms
underlying
ICI-induced
highlighted
protective
potential
reprogramming.
We
emphasize
roles
cell
macrophage
reprogramming
heart
vasculature,
showcasing
their
contributions
short-term
long-term
regulation
health.
Ultimately,
deeper
understanding
processes
will
not
only
enhance
safety
ICIs
but
also
pave
way
for
innovative
manage
cancers
therapy.
Frontiers in Oncology,
Год журнала:
2023,
Номер
13
Опубликована: Окт. 17, 2023
Objectives
Immune
checkpoint
inhibitors
(ICIs)
stimulate
antitumor
immune
responses
and,
in
parallel,
they
might
trigger
autoimmune
and
other
immunopathological
mechanisms
eventually
leading
to
immune-related
adverse
events
(irAE).
In
our
study,
we
assessed
patients
with
malignancies
who
underwent
anti-PD-1
treatment
at
the
University
of
Debrecen,
Clinical
Center.
Patients
methods
Between
June
2017
May
2021,
207
started
ICI
university.
A
total
157
received
nivolumab
50
were
treated
pembrolizumab.
We
looked
for
factors
associated
development
irAEs.
addition
correlation
studies,
performed
binary
logistic
regression
analysis
determine,
which
also
Forward
Likelihood
Ratio
(LR)
determine
independent
prognostic
factors.
Results
At
time
data
analysis,
mean
duration
was
2.03
±
0.69
years.
ROC
determined
that
9
or
more
cycles
a
significantly
higher
risk
125
≥9
cycles.
Three
times
than
Of
patients,
66
(32%)
developed
Among
irAEs,
36
(55%)
one,
23
(35%)
two,
while
7
(10%)
three
irAEs
same
patient.
The
most
common
thyroid
(33
cases),
dermatological
(25
pneumonia
(14
cases)
gastrointestinal
complications
(13
cases).
(21.8
18.7
versus
15.8
17.4;
p=0.002)
younger
start
(60.7
10.8
63.4
10.1
years;
p=0.042)
compared
without
Pembrolizumab-treated
but
less
severe
those
receiving
nivolumab.
Conclusion
is
very
effective,
however,
may
develop.
These
be
related
number
type
malignancy.
Cardiovascular Diagnosis and Therapy,
Год журнала:
2024,
Номер
14(4), С. 679 - 697
Опубликована: Авг. 1, 2024
Immune
checkpoint
inhibitors
(ICIs)
have
become
one
of
the
cornerstones
current
oncology
treatment,
and
immune
inhibitor-related
myocarditis
(IRM)
is
most
fatal
all
adverse
events
(irAEs).
Methylprednisolone
pulse
therapy
(500-1,000
mg/day)
initial
treatment
for
IRM
recommended
by
almost
relevant
guidelines.
However,
subsequent
regimens
remain
unclear
patients
who
do
not
respond
to
methylprednisolone
(who
are
defined
as
steroid-refractory
patients).
We
propose
a
potential
approach
IRM.
Immunological Reviews,
Год журнала:
2023,
Номер
318(1), С. 4 - 10
Опубликована: Авг. 26, 2023
Immune
checkpoint
inhibitors
(ICIs),
including
antibodies
targeting
anti-cytotoxic
T
lymphocyte
antigen
4
(CTLA-4),
anti-programmed
cell
death
1
(PD-1),
ligand
(PD-L1)
have
revolutionized
cancer
treatment.1,
2
Both
PD-1
and
CTLA-4
are
upregulated
upon
T-cell
activation
function
to
inhibit
peripheral
responses.
These
receptors
maintain
immune
homeostasis,
limiting
tissue
damage
during
infection
helping
prevent
autoimmune
disease.
suppresses
by
cell-extrinsic
competition
with
CD28
for
binding
the
same
ligands
cell-intrinsic
signaling
mechanisms.3
The
PD-1:PD-:L1/L2
pathway
also
responses
inhibiting
TCR/CD28
signaling,
target
lysis
cytokine
production.4
is
expressed
across
a
diverse
set
of
hematopoietic
non-hematopoietic
cells,
suggesting
it
may
more
impact
in
tissues,
whereas
its
primarily
secondary
lymphoid
organs.3
Collectively,
ICI
immunotherapy
leverages
this
latter
biology
regulate
tolerance,
allowing
system
overcome
cancer's
evasion
immunity
reestablish
ability
attack
tumor
tissues.1,
was
first
be
approved
therapy
(i.e.,
Ipilimumab)
20115-8
treat
advanced
melanoma.
Since
then,
eight
agents
PD-1/PD-L1
or
pathways
been
Food
Drug
Administration
(FDA)
over
20
types
80
indications.9
Importantly,
utilization
ICIs
adjuvant
setting
on
rise,
resulting
further
growth
number
patients
receiving
therapy.
Cancer
treated
now
anticipated
live
longer;
but
prolonged
exposure
treatment
puts
them
at
greater
risk
long-term
complications
associated
line
therapy.10-14
Unfortunately,
success
limited
emergence
treatment-induced
inflammatory
toxicities,
termed
immune-related
adverse
events
(irAEs).
irAEs
can
affect
any
organ
body
range
severity,
significant
morbidity
considerable
cost
healthcare
system.
develop
after
often
require
immunosuppressive
cessation
treatment,
thereby
potential
lifesaving
benefits
from
therapy.1,
2,
15,
16
Depending
regimen
drug
types,
combination,
doses),
66%–96%
irAEs,
7%–59%
experience
severe
irAEs.17,
18
Fulminant
fatal
irAEs—the
most
common
being
myocarditis/myositis,
pneumonitis,
neurologic
(e.g.,
Guillain–Barre
syndrome
myasthenia
gravis)—are
experienced
approximately
0.4%
anti-PD-1/PD-L1
monotherapy,
1.2%
combination
PD-1/CTLA-4
therapy.19,
Toxicities
manifest
point
they
tend
occur
frequently
within
initial
3
months
following
initiation
ICI.15,
Immuno-oncology
remains
rapidly
evolving
field,
many
co-inhibitory
beyond
likely
become
valuable
therapeutic
targets
near
future.
For
example,
relatlimab,
compound
that
blocks
(LAG-3)
has
recently
use
anti-PD1
therapy.21
This
predominantly
found
exhausted
cells
could
potentially
address
cell-related
anergy
microenvironment.
As
first-
second-line
years
come,
together
increased
as
well
increase
anti-tumor
response
efficacy
resistance,22,
23
expected
incidence
will
continue
rise
severely
limit
life-saving
ICIs.
Intriguingly,
occurring
closely
resemble
idiopathic
diseases,
rheumatoid
arthritis
(RA),
hepatitis,
bowel
disease.1
Further,
polymorphisms
various
disease
conditions—such
Type
diabetes,
thyroiditis,
Graves'
disease,
celiac
systemic
lupus
erythematosus,
arthritis15,
16,
24,
25—with
which
observed
treatment-related
share
clinical
features.
interventions
steroids,
biologics
agents,
sometimes
surgery.
Insights
into
pathogenesis
exact
trigger
timing
known,
thus
implications
not
only
care
our
understanding
diseases.
Studying
cellular
molecular
patterns
irAE
provide
rare
window
moment
when
patient's
own
starts
mounting
an
against
normal
tissue.
Such
study
enable
generating
novel
insights
mechanisms
regulation
throughout
how
tolerance.26
such,
deciphering
critical
earliest
steps
driving
sustaining
spontaneous
challenging
discern
such
diseases
fully
established.
While
we
hypothesize
onset
manipulation
breaking
tissue-specific
tolerance,1,
downstream
involved
excessive
remain
poorly
understood.
part
due
fact
preclinical
animal
models
yet
recapitulate
full
spectrum
presentations.15,
Examples
proposed
far
included
shared
antigens
between
affected
tissue,
preexisting
subclinical
inflammation,
autoantibodies,
antibody-dependent
cytotoxicity,
environmental
insults.15,
26,
27
Given
heterogeneity
breadth
presentations,
affecting
different
systems
pathological
drivers.
Among
sharing
similar
histological
characteristics
specific
possible
multiple
mechanistic
endotypes
result
comparable
manifestations.
Our
restricted
development
targeted
solutions.
Hitherto,
management
guidelines
developed
almost
entirely
based
small
retrospective
studies
expert
opinion.
Because
toxicity
severity
differ,
medical
community
conceive
prospective
trials
each
individually,
opposed
studying
together.
Over
last
few
years,
progress
made
biological
drivers
ICI-related
developing
effective
mitigation
strategies.
Further
research
underpinning
define
better
predictors
prevention
their
occurrence,
new,
targeted,
improved
solutions
mitigate
these
toxicities
while
preserving
response.
issue
comprises
compilation
13
review
pieces
top
scientists
experts
field
who
discuss
current
systems.
Reviews
include
several
in-depth
overviews
presentations.
They
relationship
response,
discussions
available
mechanisms.
cover
predictive
biomarkers
genetic
factors
identified
to-date,
strategies
used,
using
candidates
intended
improve
patient
outcomes.
reviews
summarize
state-of-the
complex
subject,
challenges
therapies
posed
along
opened
questions
should
focus
future
investigations.
six
delves
deeply
organ-specific
irAEs.
It
crucial
understand
immunopathology
organ-systems
allow
personalized
suppression
spare
negative
effects
immunity.
Although
system,
barrier
gastrointestinal
tract,
skin,
liver,
lungs,15,
26
three
reviews.
organs
so
commonly
suggests
antigenic
commensal
microbiome,
though
demonstrated.
One
reported
vitiligo,
condition
characterized
immune-mediated
destruction
melanocytes
melanoma
undergoing
going
immunotherapies.15,
Vitiligo
driven
melanocyte
antigens,
produced
leads
melanocytes,
characteristic
depigmentation
individuals.28
early
observations,
originally
hypothesized
other
might
healthy
malignant
similarly
vitiligo.
Nonetheless,
majority
particular
type
cast
doubt
hypothesis.
Alternative
hypotheses
emerged
discussed
posit
role
tissue-resident
memory
(TRM
cells),
long-lived
effectors
reside
tissues
make
up
TRM
express
molecules
control
activation.
play
important
roles
surveillance
recall
pathogens.29-31
Recent
investigated
whether
triggers
promoting
expansion
local
resident
cells.
work
covering
track,
lung.
Michael
Dougan
provides
comprehensive
(GI)
caused
ICIs.32
GI
mild
nature,
high
occurrence
rate
makes
leading
cause
In
his
review,
he
description
manifestations
thorough
discussion
known
to-date
gut
CD8+
TRMs)
ICI-colitis,
ICIs.33
He
discusses
standard
care,
upcoming
trials,
related
lack
trial
data
guide
care.
highlights
unanswered
investigation.
second
Blair
Allais
colleagues
focused
dermatologic
reported,
visible,
among
seen
therapy.34
cutaneous
(cirAEs)
mild,
presentations
occur.35
et
al.
clear
what
about
cirAEs
through
lenses
used
them.
harnessing
power
large
datasets
association
establish
definitions
cirAEs,
need
therapies.
describe
leveraging
infer
immunosuppression
managing
opportunities
help
Fiamma
Berner
Lukas
Flatz
two
emerging
classes
self-antigens
skin
pneumonitis
non-small
lung
therapy.36
self-antigen-specific
believed
dual
mediating
lung,
creates
challenge
distinguishing
signature
those
methods
identification
self-antigen
tumors.
Finally
lead
successful
absence
problematic
Gary
Reynolds
rheumatological
disabling,
evolve
chronic.37
superficially
features
rheumatic
(IMRDs),38
arthritis,
psoriatic
Sjogren's
syndrome,
polymyalgia
rheumatica.
parallels
differences
IMRDs,
highlight
that,
knowledge,
clinically
immunologically
distinct
entities.
Harish
Seethapathy,
Kavita
Mistry,
Meghan
Sise
elegantly
kidney,
present
acute
interstitial
nephritis
(ICI-AIN).39
thoroughly
explore
manifestation
ICI-AIN
distinctive
presentation
compared
conventional
drug-induced
AIN.
authors
detailed
ICI-AIN,
underscore
diagnostic
arise
findings.
To
conclude
section
issue,
Jingyi
Gong,
Tomas
Neilan,
Daniel
A.
Zlotoff
myocarditis
(irMyocarditis),
which,
all
cardiovascular
extensively
studied
substantial
mortality.40
irMyocarditis
occurs
1%
recipients,
rising
increasing
regimens
patients.19-21,
41-43
20%–40%
cases,
10-fold
higher
than
non-ICI
lymphocytic
myocarditis.41-44
Nearly
half
cases
major
cardiac
events,
arrhythmias,
cardiogenic
shock,
sudden
death.41-44
Furthermore,
near-absolute
contraindication
therapy,
turn
harm
oncologic
prognosis.45
frame
around
primary
objectives.
First,
summary
pathogenesis,
compare
myocardial
examine
categories:
mediators,
participating
signals
soluble
factors,
receptor
(TCR)
clonality
specificity.
Second,
explaining
heightened
forms
inflammation
why
affects
elegant
highlighting
knowledge
gaps
requiring
investigation
above
next
includes
four
delve
drivers,
autoimmunity,
leveraged
underpinnings.
defining
underlying
presents
opportunity
alleviate
detrimental
side
itself.
Namrata
Singh,
Anne
Hocking,
Jane
Buckner
interesting
intersection
diseases.46
phenocopy
well-defined
unclear
truly
especially
ICI-associated
fulminate.47
explores
responsible
inducing
focusing
ICI-diabetes,
ICI-thyroiditis,
ICI-arthritis.
genetics
autoantibodies
single-cell
genomic
enabled
signatures
Ultimately,
holds
importance
terms
basic
implications.
Indeed,
science
standpoint,
elucidating
connection
generate
fundamental
autoimmunity
principles
tolerance
human.
From
perspective,
unraveling
nominate
already
autoimmunity.
Dhodapkar,
Alyssa
Duffy,
Madhav
Dhodapkar
inhibitor
B-cell
drive
alterations
compartments.48
Their
involvement
humoral
immunity,
subsets
ICI.
invest
resources
investigating
cross
talk
B
drives
pathogenic
contributing
Noah
Earland
lay
out
perspective49
published
analyzed
cohort
multimodal
strategy
involving
RNA
sequencing,
mass
cytometry
blood
identify
development.50
showed
TCR
diversity
circulating
levels
activated
CD4
effector
both
independent
affected.50
Through
contextualize
results
comparison
blood-based
biomarkers.
links
contribute
development,
autoreactive
located
site
toxicity.
Finally,
considered
empower
translation
findings
irAE-related
tests.
Presently,
pathophysiological
understood
because
mouse
underestimate
experience,51
do
accurately
replicate
aspects
human
biology.15,
52-54
Nevertheless,
there
multitude
tailored
model
patients.
manuscript
section,
Morgan
Cina,
Jessica
Venegas,
Arabella
Young
put
very
capture
some
etiology
underpinnings
responses.55
contexts
useful,
improved,
advantages
disadvantages
Approaches
silico
modeling
datasets,
vitro
organoid
models,
vivo
non-human
primate
canine
progressed
rapidly.
Particularly
efforts
invested
establishing
end
discussing
new
fidelity
Better
ultimately
treatments.
third
determine
ICI,
predict
predisposed
step
towards
prophylactic
prove
making
informed
decisions
regarding
tailoring
options
patient.
uncovering
germline
susceptibility
variants
reviewed
Alexander
Gusev.56
sporadic
linked
would
heritable.57-59
summarizes
mapping
outcome,
perspectives
group
genome-wide
analysis
IL7
irAEs,60
were
subsequently
independently
replicated.61
extant
leverage
etiology,
addition
improving
predicting
There
currently
no
FDA
whom
suffering
outweighed
Moreover,
predictable
treatments,
chemotherapy
therapy.62
map
selection,
prevention,
monitoring
initiated.
Rachel
Goodman,
Seungyeon
Jung,
Justin
Balko,
Douglas
Johnson.63
categories,
help:
(i)
stratify
pre-treatment
subjects
toxicities;
(ii)
diagnose
cases;
(iii)
course.
decision-making,
alter
course
frequency
monitoring.
We
Steven
M.
Blum,
Sherin
Rouhani,
Ryan
Sullivan
treatments
modulating
response.64
complex65
influenced
irAE-affected
organ,
histology,
individual
characteristics.
maximize
minimizing
host
environments,
essential
landscape
populations
significantly
changed
since
approval
metastatic
2011;
indications
curative
intent.
malignancies
like
melanoma,
largely
before
introduction
surpass
risks
patients,
acceptable.
context
neoadjuvant
risk-to-benefit
ratio
less
straightforward;
disease-free
survival,
note
proportion
achieve
remission
without
ICIs,
reevaluate
versus
reward
cancer-free.
illustration
(Figure
1)
captures
complicated
balance
Despite
remember
drugs
resulted
good
news
stories,
providing
hopes
With
population,
becoming
increasingly
support
aimed
root
mitigated
evolved
remaining
answered
as,
determining
experiencing
irAEs?
Can
What
certain
systems?
How
related?
Which
influence
patient,
transient
chronic
fatal?
choose
sparing
response?
Once
redeveloping
safely
rechallenged
therapy?
Answering
outstanding
immuno-oncology
field.
Lastly,
broad
theme
emerges
financial
disciplines
cross-institutional
multidisciplinary
teams
spanning
systems,
academic
researchers,
federal
agencies,
commercial
partners,
advocacy
groups
solve
integrate
discoveries
sustainable
applications.
Even
once
identified,
still
necessitate
collaborative
endeavors
infrastructure
required
evaluating
owe
find
order
quality
life
optimally
benefit
virtues
ICI-therapy
fight
cancers.
I
wish
thank
Dr.
John
Cambier
manuscripts
helpful
comments.
Isabela
Kernin
her
conceptualizing
figure
Claudia
Bentley
creating
figure.
ACV
paid
consultant
Bristol
Myers
Squibb.
funded
National
Institute
Health
Director's
New
Innovator
Award
(DP2CA247831),
Damon
Runyon-Rachleff
Innovation
Award,
Melanoma
Research
Alliance
Investigator
(https://doi.org/10.48050/pc.gr.143739),
Massachusetts
General
Hospital
(MGH)
Transformative
Scholar
Medicine
MGH
Howard
Goodman
Fellowship.
Data
applicable
article.
Postgraduate Medical Journal,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 25, 2024
Abstract
Background
Immune
checkpoint
inhibitors
(ICIs)
are
widely
used
in
cancer
treatment;
however,
the
emergence
of
ICI-associated
myocarditis
(ICI-MC)
presents
a
severe
and
potentially
fatal
complication
with
poorly
understood
pathophysiological
mechanisms.
This
study
aimed
to
identify
crucial
immune-related
genes
ICI-MC
uncover
potential
therapeutic
targets
using
bioinformatics.
Methods
Using
GSE180045
dataset,
which
includes
three
groups—Group
A:
ICI
patients
without
immune
adverse
events,
Group
B:
non-myocarditis
C:
myocarditis—we
analyzed
differentially
expressed
(DEGs)
between
samples
(Group
C)
controls
(Groups
A
B).
These
DEGs
were
then
cross-referenced
1796
from
immPort
database
DEGs.
We
conducted
functional
enrichment
analyses
(Gene
Ontology,
Kyoto
Encyclopedia
Genes
Genomes,
gene
set
analysis),
constructed
protein–protein
interaction
network,
identified
hub
genes.
Validation
GSE4172
dataset
led
identification
optimal
feature
overlap
Predictions
target
MicroRNAs
(miRNAs)
made,
competing
endogenous
RNA
(ceRNA)
network
was
constructed.
Target
drugs
for
predicted
Connectivity
Map
database.
Results
58
controls,
32
after
intersection
Functional
revealed
cell
lysis,
CD8+
T-cell
receptor,
natural
killer
cell–mediated
cytotoxicity,
RAGE
signaling.
Notably
upregulated
included
IL7R,
PRF1,
GNLY,
CD3G,
NKG7,
GZMH,
GZMB,
KLRB1,
KLRK1,
CD247.
In
validation
407
uncovered,
resulting
3
(KLRB1,
GZMH).
The
miRNAs,
lincRNAs,
circRNAs
constituted
comprehensive
ceRNA
network.
Among
top
10
elevated
connectivity
scores
acetohydroxamic
acid,
indicating
need
caution
treatment.
Conclusion
KG7,
KLRB1
as
pivotal
ICI-MC.
Biological
enrichments
pathways
involved
receptor
pathway,
signaling,
proinflammatory
responses.
illuminated
role
critical
molecules
underscored
importance
avoiding
such
acid
Key
message
What
is
already
known
on
this
topic
Myocarditis
recognized
serious
toxicity,
seemingly
infrequent
yet
often
fulminant
lethal.
underlying
mechanisms
remain
not
fully
understood.
Although
significance
T
cells
cytotoxic
lymphocyte–associated
protein
4
(CTLA-4)
evident,
inciting
antigens,
reasons
their
recognition,
causing
cardiac
injury
well
characterized.
An
improved
understanding
will
provide
insights
into
equilibrium
cardiovascular
systems.
adds
Our
further
validates
CTLA-4
myocarditis.
More
importantly,
we
genes—NKG7,
KLRB1—essential
development
proposed
networks
involving
these
key
How
might
affect
research,
practice
or
policy
newly
discovered
intricate
molecular
interactions
offer
perspective
Furthermore,
our
findings
advise
regarding
use
like
during
As
regulatory
deepens,
provides
valuable
that
could
inform
future
strategies