Molecular mimicry as a mechanism of viral immune evasion and autoimmunity
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Окт. 30, 2024
Язык: Английский
Unlocking the secrets of the immunopeptidome: MHC molecules, ncRNA peptides, and vesicles in immune response
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Янв. 29, 2025
The
immunopeptidome,
a
diverse
set
of
peptides
presented
by
Major
Histocompatibility
Complex
(MHC)
molecules,
is
critical
component
immune
recognition
and
response.
This
review
article
delves
into
the
mechanisms
peptide
presentation
MHC
particularly
emphasizing
roles
ncRNA-derived
extracellular
vesicles
(EVs)
in
shaping
immunopeptidome
landscape.
We
explore
established
emerging
insights
molecule
interactions
with
peptides,
including
dynamics
loading,
transport,
influence
cellular
genetic
variations.
highlights
novel
research
on
non-coding
RNA
(ncRNA)-derived
which
challenge
conventional
views
antigen
processing
role
EVs
transporting
these
thereby
modulating
responses
at
remote
body
sites.
not
only
challenges
but
also
opens
up
new
avenues
for
understanding
responses.
Furthermore,
we
discuss
implications
developing
therapeutic
strategies,
cancer
immunotherapy.
By
conducting
comprehensive
analysis
current
literature
advanced
methodologies
immunopeptidomics,
this
aims
to
deepen
complex
interplay
between
system,
offering
perspectives
potential
diagnostic
applications.
Additionally,
provide
mechanism
enhanced
surface
highlight
pathway
their
systemic
distribution,
potentially
altering
surveillance
landscapes.
Язык: Английский
Harnessing nanoparticles for reshaping tumor immune microenvironment of hepatocellular carcinoma
Discover Oncology,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 5, 2025
Hepatocellular
carcinoma
(HCC)
is
one
of
the
most
prevalent
cancers,
characterized
by
high
morbidity
and
mortality
rates.
Recently,
immunotherapy
has
emerged
as
a
crucial
treatment
modality
for
HCC,
following
surgery,
locoregional
therapies,
targeted
therapies.
This
approach
harnesses
body's
immune
system
to
target
eliminate
cancer
cells,
potentially
resulting
in
durable
antitumor
responses.
However,
acquired
resistance
tumor
immunosuppressive
microenvironment
(TIME)
significantly
hinder
its
clinical
application.
advancements
nanotechnology,
coupled
with
deeper
understanding
biology
nano-biological
interactions,
have
led
development
various
nanoparticles
aimed
at
enhancing
therapeutic
efficacy
through
specific
targeting
tissues.
These
increase
accumulation
immunotherapeutic
drugs
within
microenvironment,
thereby
transforming
TIME.
In
this
review,
we
provide
concise
overview
fundamental
principles
governing
TIME
landscape
HCC
discuss
rationale
applications
context.
Additionally,
highlight
existing
challenges
potential
opportunities
translation
nanomedicines.
Язык: Английский
Alternative Splicing as a Modulator of the Interferon-Gamma Pathway
Cancers,
Год журнала:
2025,
Номер
17(4), С. 594 - 594
Опубликована: Фев. 10, 2025
Interferon-gamma
(IFN-γ)
is
a
critical
cytokine
that
plays
pivotal
role
in
immune
system
regulation.
It
key
mediator
of
both
cellular
defense
mechanisms
and
antitumor
immunity.
As
the
sole
member
type
II
interferon
family,
IFN-γ
modulates
responses
by
activating
macrophages,
enhancing
natural
killer
cell
function,
regulating
gene
expression
across
multiple
processes.
Alternative
splicing
post-transcriptional
regulatory
mechanism
generates
mature
messenger
RNAs
from
single
gene,
dramatically
increasing
proteome
diversity
without
need
proportional
genome
expansion.
This
process
occurs
90–95%
human
genes,
with
alternative
events
allowing
for
production
diverse
protein
isoforms
can
have
distinct—or
even
opposing—functional
properties.
crucial
cancer
immunology,
potentially
generating
tumor
neoepitopes
modulating
responses.
However,
how
affects
IFN-γ’s
activity
still
poorly
understood.
review
explores
regulates
function
upstream
regulators
downstream
effectors
IFN-γ,
revealing
complex
response
modulation.
Key
transcription
factors
signaling
molecules
pathway
are
alternatively
spliced,
alter
signaling,
to
environmental
cues.
Specific
splice
variants
enhance
or
inhibit
IFN-γ-mediated
responses,
influencing
immunotherapy,
autoimmune
conditions,
infectious
disease
outcomes.
The
emerging
understanding
these
offers
promising
therapeutic
strategies
manipulating
through
targeted
molecular
interventions.
Язык: Английский
Advancements and challenges in personalized neoantigen-based cancer vaccines
Oncology Reviews,
Год журнала:
2025,
Номер
19
Опубликована: Март 14, 2025
Advancements
in
personalized
neoantigen-based
cancer
vaccines
are
ushering
a
new
era
oncology,
targeting
unique
genetic
alterations
within
tumors
to
enhance
treatment
precision
and
efficacy.
Neoantigens,
specific
cells
absent
normal
tissues,
at
the
heart
of
these
vaccines,
promising
direct
immune
system
specifically
against
tumor,
thereby
maximizing
therapeutic
efficacy
while
minimizing
side
effects.
The
identification
neoantigens
through
genomic
proteomic
technologies
is
central
developing
allowing
for
precise
mapping
tumor's
mutational
landscape.
Despite
advancements,
accurately
predicting
which
will
elicit
strong
responses
remains
challenging
due
tumor
variability
complexity
interactions.
This
necessitates
further
refinement
bioinformatics
tools
predictive
models.
Moreover,
heavily
depends
on
innovative
delivery
methods
that
neoantigen
presentation
system.
Techniques
like
encapsulating
lipid
nanoparticles
using
viral
vectors
critical
improving
vaccine
stability
delivery.
Additionally,
contribute
towards
achieving
Sustainable
Development
Goal
3.8,
promoting
universal
health
coverage
by
advancing
access
safe
effective
treatments.
review
delves
into
potential
transform
treatment,
examining
both
revolutionary
advancements
ongoing
challenges
they
face.
Язык: Английский
Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Март 26, 2025
Periodontal
pathogen
Porphyromonas
gingivalis
(P.
gingivalis)
is
believed
to
possess
immune
evasion
capabilities,
but
it
remains
unclear
whether
this
related
host
gene
alternative
splicing
(AS).
In
study,
RNA-sequencing
revealed
significant
changes
in
both
AS
landscape
and
transcriptomic
profile
of
macrophages
following
P.
infection
with/without
knockout
gingipain
(a
unique
toxic
protease
gingivalis).
increased
the
PD-L1
transcripts
expression
selectively
upregulated
a
specific
coding
isoform
that
more
effectively
binds
PD-1
on
T
cells,
thereby
inhibiting
function.
Biological
experiments
also
detected
switch
gingivalis-infected
or
gingipain-treated
macrophages.
AlphaFold
3
predictions
indicated
protein
docking
compatibility
between
gingivalis-upregulated
was
over
80%
higher
than
another
isoform.
These
findings
suggest
employs
modulate
PD-L1,
facilitating
evasion.
Язык: Английский
Harnessing antibody-mediated recognition of the intracellular proteome with T cell receptor-like specificity
Maya Haus‐Cohen,
Yoram Reiter
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Ноя. 22, 2024
The
clinical
success
of
cancer
immunotherapy
has
driven
ongoing
efforts
to
identify
novel
targets
that
can
effectively
guide
potent
effector
functions
eliminate
malignant
cells.
Traditionally,
immunotherapies
have
focused
on
surface
antigens;
however,
these
represent
only
a
small
fraction
the
proteome,
limiting
their
therapeutic
potential.
In
contrast,
majority
proteins
within
human
proteome
are
intracellular,
yet
they
represented
cell
as
short
peptides
presented
by
MHC
class
I
molecules.
These
peptide-MHC
complexes
offer
vast
and
largely
untapped
resource
for
targets.
intracellular
including
neo-antigens,
presents
an
exciting
opportunity
development
cell-based
soluble
immunotherapies.
Targeting
intracellular-derived
molecules
surfaces
be
achieved
using
specific
T-cell
receptors
(TCRs)
or
TCR-mimicking
antibodies,
known
TCR-like
(TCRL)
antibodies.
Current
strategies
under
investigation
include
adoptive
transfer
TCR-engineered
TCRL-T
cells
CAR-T
target
complexes,
well
TCR-
TCRL-based
agents
like
bispecific
T
engagers.
Recent
developments
in
targeting
TCRL-
TCR-based
shown
promising
results,
with
two
therapies
recently
receiving
FDA
approval
treatment
unresectable
metastatic
uveal
melanoma
synovial
sarcoma.
This
review
focuses
processes
selecting
isolating
moieties,
emphasis
pre-clinical
studies
explore
potential
immunotherapy.
Язык: Английский
Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 29, 2024
Abstract
Periodontal
pathogen
Porphyromonas
gingivalis(
Pg)
is
believed
to
possess
immune
evasion
capabilities,
but
it
remains
unclear
whether
this
related
host
gene
alternative
splicing
(AS).
In
study,
RNA-sequencing
(RNA-seq)
revealed
significant
changes
in
both
AS
landscape
and
transcriptomic
profile
of
macrophages
following
Pg
infection
with/without
knockout
gingipain
(a
unique
toxic
protease
Pg).
increased
the
programmed
death
ligand
1
(PD-L1)
transcripts
expression
selectively
upregulated
a
specific
coding
isoform
that
more
effectively
binds
cell
protein
(PD-1)
receptors
on
T
cells,
thereby
inhibiting
function.
Biological
experiments
confirmed
these
results
demonstrated
switch
PD-L1
was
gingipain-dependent.
AlphaFold
3
predictions
indicated
docking
compatibility
between
PD-1
Pg-upregulated
over
80%
higher
than
another
isoform.
These
findings
suggest
Pg
employs
modulate
PD-L1,
facilitating
evasion.
Язык: Английский
The role of splicing events in the inflammatory response of atherosclerosis: molecular mechanisms and modulation
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Дек. 17, 2024
Atherosclerosis
is
a
chronic
inflammatory
disease
characterized
by
persistent
responses
throughout
all
stages
of
its
progression.
Modulating
these
promising
avenue
for
the
development
cardiovascular
therapies.
Splicing
events
modulate
gene
expression
and
diversify
protein
functionality,
exerting
pivotal
roles
in
mechanisms
underlying
atherosclerosis.
These
insights
may
provide
novel
opportunities
developing
anti-inflammatory
therapies
this
disease.
This
article
systematically
discusses
diverse
splice
variants
how
splicing
impact
response
atherosclerosis
via
endothelial
cells,
macrophages,
vascular
smooth
muscle
highlighting
their
molecular
implications.
Furthermore,
study
summarizes
clinical
evidence
supporting
splicing-related
molecules
as
diagnostic
biomarkers
therapeutic
targets
Lastly,
we
outline
current
challenges
future
research
directions
concerning
offers
perspective
formulating
new
strategies
aimed
at
lowering
risk
Язык: Английский