Recent
advances
in
neoantigen
research
have
accelerated
the
development
of
tumor
immunotherapies,
including
adoptive
cell
therapies
(ACTs),
cancer
vaccines
and
antibody-based
therapies,
particularly
for
solid
tumors.
With
next-generation
sequencing
bioinformatics
technology,
rapid
identification
prediction
tumor-specific
antigens
(TSAs)
has
become
possible.
Compared
with
tumor-associated
(TAAs),
highly
immunogenic
TSAs
provide
new
targets
personalized
immunotherapy
can
be
used
as
prospective
indicators
predicting
patient
survival,
prognosis,
immune
checkpoint
blockade
response.
Here,
characterization
neoantigens
clinical
application
neoantigen-based
TCR-T
strategies
are
summarized,
current
status,
inherent
challenges,
translational
potential
these
discussed.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Янв. 6, 2023
Abstract
Recent
advances
in
neoantigen
research
have
accelerated
the
development
and
regulatory
approval
of
tumor
immunotherapies,
including
cancer
vaccines,
adoptive
cell
therapy
antibody-based
therapies,
especially
for
solid
tumors.
Neoantigens
are
newly
formed
antigens
generated
by
cells
as
a
result
various
tumor-specific
alterations,
such
genomic
mutation,
dysregulated
RNA
splicing,
disordered
post-translational
modification,
integrated
viral
open
reading
frames.
recognized
non-self
trigger
an
immune
response
that
is
not
subject
to
central
peripheral
tolerance.
The
quick
identification
prediction
neoantigens
been
made
possible
advanced
next-generation
sequencing
bioinformatic
technologies.
Compared
tumor-associated
antigens,
highly
immunogenic
provide
emerging
targets
personalized
serve
prospective
predictors
survival
prognosis
checkpoint
blockade
responses.
therapies
will
be
aided
understanding
mechanism
underlying
neoantigen-induced
anti-tumor
streamlining
process
neoantigen-based
immunotherapies.
This
review
provides
overview
on
characterization
outlines
clinical
applications
immunotherapeutic
strategies
based
neoantigens.
We
also
explore
their
current
status,
inherent
challenges,
translation
potential.
Proceedings of the National Academy of Sciences,
Год журнала:
2020,
Номер
117(33), С. 20159 - 20170
Опубликована: Авг. 3, 2020
Significance
N
6
-methylation
of
adenosine
(m
A)
RNA
modification
plays
important
roles
in
development
and
tumorigenesis.
The
functions
mechanisms
m
A
demethylases
during
cancer
immunotherapy
is
still
unclear.
Here
we
employed
melanoma
colon
syngeneic
mouse
models
to
study
the
ALKBH5
FTO
anti–PD-1
antibody
GVAX
vaccination
therapy.
We
found
that
knockout
tumor
cells
enhances
efficacy
prolonged
survival.
modulates
target
gene
expression
splicing,
leading
changes
metabolite
contents,
such
as
lactate
microenvironment,
which
regulates
suppressive
lymphocytes
Treg
myeloid-derived
suppressor
cell
accumulations.
Importantly,
by
using
ALKBH5-specific
inhibitor,
observed
similar
phenotype,
indicating
future
translational
application
our
findings.
Nature Biotechnology,
Год журнала:
2022,
Номер
40(8), С. 1231 - 1240
Опубликована: Май 19, 2022
Despite
the
availabilty
of
imaging-based
and
mass-spectrometry-based
methods
for
spatial
proteomics,
a
key
challenge
remains
connecting
images
with
single-cell-resolution
protein
abundance
measurements.
Here,
we
introduce
Deep
Visual
Proteomics
(DVP),
which
combines
artificial-intelligence-driven
image
analysis
cellular
phenotypes
automated
single-cell
or
single-nucleus
laser
microdissection
ultra-high-sensitivity
mass
spectrometry.
DVP
links
to
complex
subcellular
while
preserving
context.
By
individually
excising
nuclei
from
cell
culture,
classified
distinct
states
proteomic
profiles
defined
by
known
uncharacterized
proteins.
In
an
archived
primary
melanoma
tissue,
identified
spatially
resolved
proteome
changes
as
normal
melanocytes
transition
fully
invasive
melanoma,
revealing
pathways
that
change
in
manner
cancer
progresses,
such
mRNA
splicing
dysregulation
metastatic
vertical
growth
coincides
reduced
interferon
signaling
antigen
presentation.
The
ability
retain
precise
information
tissue
context
has
implications
molecular
profiling
clinical
samples.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Фев. 24, 2021
Abstract
The
abnormal
regulation
of
alternative
splicing
is
usually
accompanied
by
the
occurrence
and
development
tumors,
which
would
produce
multiple
different
isoforms
diversify
protein
expression.
aim
present
study
was
to
conduct
a
systematic
review
in
order
describe
regulatory
mechanisms
splicing,
as
well
its
functions
tumor
cells,
from
proliferation
apoptosis
invasion
metastasis,
angiogenesis
metabolism.
events
contributed
progression
oncogenic
drivers
and/or
bystander
factors.
alterations
factors
detected
tumors
other
mis-splicing
(i.e.,
long
non-coding
circular
RNAs)
tumorigenesis
were
also
included.
findings
recent
therapeutic
approaches
targeting
catalysis
proteins
modulate
pathogenically
spliced
(including
tumor-specific
neo-antigens
for
cancer
immunotherapy)
introduced.
emerging
RNA-based
strategies
treatment
with
abnormally
discussed.
However,
further
studies
are
still
required
address
association
between
more
detail.
Journal of Hematology & Oncology,
Год журнала:
2020,
Номер
13(1)
Опубликована: Июль 11, 2020
Abstract
RNA-binding
protein
(RBP)
has
a
highly
dynamic
spatiotemporal
regulation
process
and
important
biological
functions.
They
are
critical
to
maintain
the
transcriptome
through
post-transcriptionally
controlling
processing
transportation
of
RNA,
including
regulating
RNA
splicing,
polyadenylation,
mRNA
stability,
localization,
translation.
Alteration
each
will
affect
life
cycle,
produce
abnormal
phenotypes,
thus
lead
occurrence
development
tumors.
Here,
we
summarize
RBPs
involved
in
tumor
progression
underlying
molecular
mechanisms
whereby
they
regulated
exert
their
effects.
This
analysis
is
an
step
towards
comprehensive
characterization
post-transcriptional
gene
progression.
A
modified
Chromium
10x
droplet-based
protocol
that
subsamples
cells
for
both
short-read
and
long-read
(nanopore)
sequencing
together
with
a
new
computational
pipeline
(FLAMES)
is
developed
to
enable
isoform
discovery,
splicing
analysis,
mutation
detection
in
single
cells.
We
identify
thousands
of
unannotated
isoforms
find
conserved
functional
modules
are
enriched
alternative
transcript
usage
different
cell
types
species,
including
ribosome
biogenesis
mRNA
splicing.
Analysis
at
the
level
allows
data
integration
scATAC-seq
on
individual
promoters,
improved
correlation
protein
expression
data,
linked
mutations
known
confer
drug
resistance
transcriptome
heterogeneity.
