Science,
Journal Year:
2024,
Volume and Issue:
384(6695)
Published: May 2, 2024
B
lymphocytes
are
essential
mediators
of
humoral
immunity
and
play
multiple
roles
in
human
cancer.
To
decode
the
functions
tumor-infiltrating
cells,
we
generated
a
cell
blueprint
encompassing
single-cell
transcriptome,
cell-receptor
repertoire,
chromatin
accessibility
data
across
20
different
cancer
types
(477
samples,
269
patients).
cells
harbored
extraordinary
heterogeneity
comprised
15
subsets,
which
could
be
grouped
into
two
independent
developmental
paths
(extrafollicular
versus
germinal
center).
Tumor
extrafollicular
pathway
were
linked
with
worse
clinical
outcomes
resistance
to
immunotherapy.
The
dysfunctional
program
was
associated
glutamine-derived
metabolites
through
epigenetic-metabolic
cross-talk,
promoted
T
cell-driven
immunosuppressive
program.
These
suggest
an
intratumor
balance
between
germinal-center
responses
that
possibly
harnessed
for
cell-targeting
Briefings in Bioinformatics,
Journal Year:
2022,
Volume and Issue:
23(4)
Published: July 5, 2022
Abstract
Complex
biomedical
data
generated
during
clinical,
omics
and
mechanism-based
experiments
have
increasingly
been
exploited
through
cloud-
visualization-based
mining
techniques.
However,
the
scientific
community
still
lacks
an
easy-to-use
web
service
for
comprehensive
visualization
of
data,
particularly
high-quality
publication-ready
graphics
that
allow
easy
scaling
updatability
according
to
user
demands.
Therefore,
we
propose
a
community-driven
modern
service,
Hiplot
(https://hiplot.org),
with
concise
top-quality
applications
life
sciences
fields.
This
permits
users
conveniently
interactively
complete
few
specialized
tasks
previously
could
only
be
conducted
by
senior
bioinformatics
or
biostatistics
researchers.
It
covers
most
daily
demands
researchers
its
equipped
240+
functions,
involving
basic
statistics,
multi-omics,
regression,
clustering,
dimensional
reduction,
meta-analysis,
survival
analysis,
risk
modelling,
etc.
Moreover,
improve
efficiency
in
use
development
plugins,
introduced
some
core
advantages
on
client-/server-side
website,
such
as
spreadsheet-based
importing,
cross-platform
command-line
controller
(Hctl),
multi-user
plumber
workers,
JavaScript
Object
Notation-based
plugin
system,
data/parameters,
results
errors
reproduction
real-time
updates
mode.
Meanwhile,
using
demo/real
sets
benchmark
tests,
explored
statistical
parameters,
cancer
genomic
landscapes,
disease
factors
performance
website
based
selected
native
plugins.
The
statistics
visits
numbers
further
reflect
potential
impact
this
relevant
Thus,
devoted
would
benefit
from
emerging
free
service.
Genome Medicine,
Journal Year:
2019,
Volume and Issue:
11(1)
Published: Aug. 28, 2019
Neoantigens
are
newly
formed
peptides
created
from
somatic
mutations
that
capable
of
inducing
tumor-specific
T
cell
recognition.
Recently,
researchers
and
clinicians
have
leveraged
next
generation
sequencing
technologies
to
identify
neoantigens
create
personalized
immunotherapies
for
cancer
treatment.
To
a
vaccine,
must
be
computationally
predicted
matched
tumor-normal
data,
then
ranked
according
their
capability
in
stimulating
response.
This
candidate
neoantigen
prediction
process
involves
multiple
steps,
including
mutation
identification,
HLA
typing,
peptide
processing,
peptide-MHC
binding
prediction.
The
general
workflow
has
been
utilized
many
preclinical
clinical
trials,
but
there
is
no
current
consensus
approach
few
established
best
practices.
In
this
article,
we
review
recent
discoveries,
summarize
the
available
computational
tools,
provide
analysis
considerations
each
step,
prediction,
prioritization,
delivery,
validation
methods.
addition
reviewing
state
analysis,
practical
guidance,
specific
recommendations,
extensive
discussion
critical
concepts
points
confusion
practice
characterization
use.
Finally,
outline
necessary
areas
development,
need
improve
class
II
typing
accuracy,
expand
software
support
diverse
sources,
incorporate
response
data
algorithms.
ultimate
goal
workflows
vaccines
patient
outcomes
types.
Nature Communications,
Journal Year:
2019,
Volume and Issue:
10(1)
Published: Aug. 20, 2019
Abstract
The
worldwide
incidence
of
pulmonary
carcinoids
is
increasing,
but
little
known
about
their
molecular
characteristics.
Through
machine
learning
and
multi-omics
factor
analysis,
we
compare
contrast
the
genomic
profiles
116
(including
35
atypical),
75
large-cell
neuroendocrine
carcinomas
(LCNEC),
66
small-cell
lung
cancers.
Here
report
that
integrative
analyses
on
257
neoplasms
stratify
atypical
into
two
prognostic
groups
with
a
10-year
overall
survival
88%
27%,
respectively.
We
identify
therapeutically
relevant
carcinoids,
suggesting
DLL3
immune
system
as
candidate
therapeutic
targets;
confirm
value
OTP
expression
levels
for
prognosis
diagnosis
these
diseases,
unveil
group
supra-carcinoids.
This
comprises
samples
carcinoid-like
morphology
yet
clinical
features
deadly
LCNEC,
further
supporting
previously
proposed
link
between
low-
high-grade
neoplasms.
Frontiers in Immunology,
Journal Year:
2022,
Volume and Issue:
12
Published: Jan. 7, 2022
In
the
last
decade,
treatment
of
non-small
cell
lung
cancer
(NSCLC)
has
been
revolutionized
by
introduction
immune
checkpoint
inhibitors
(ICI)
directed
against
programmed
death
protein
1
(PD-1)
and
its
ligand
(PD-L1),
or
cytotoxic
T
lymphocyte
antigen
4
(CTLA-4).
spite
these
improvements,
some
patients
do
not
achieve
any
benefit
from
ICI,
inevitably
develop
resistance
to
therapy
over
time.
Tumor
microenvironment
(TME)
might
influence
response
immunotherapy
due
prominent
role
in
multiple
interactions
between
neoplastic
cells
system.
Studies
investigating
perspective
TME
pointed
out
a
complex
scenario
where
tumor
angiogenesis,
soluble
factors,
suppressive/regulatory
elements
composing
itself
participate
growth.
this
review,
we
point
current
state
knowledge
involving
relationship
components
NSCLC
as
well
their
with
providing
an
update
on
novel
predictors
currently
employed
ICI
new
therapeutic
targets
investigational
agents.
first
place,
increasing
evidence
suggests
that
represent
promising
biomarker
sensitivity
based
presence
immune-modulating
cells,
such
Treg,
myeloid
derived
suppressor
associated
macrophages,
which
are
known
induce
immunosuppressive
environment,
poorly
responsive
ICI.
Consequently,
clinical
studies
have
designed
towards
pro-immunogenic
subsequently
improve
activity
Currently,
mostly
approach
relies
association
“classic”
targeting
PD-1/PD-L1
agents
molecules,
LAG-3
TIM-3.
To
date,
trials
already
shown
results,
while
multitude
prospective
ongoing,
results
significantly
future
immunotherapy.
Clinical Cancer Research,
Journal Year:
2022,
Volume and Issue:
28(12), P. 2704 - 2714
Published: March 18, 2022
KRAS
mutation
(MT)
is
a
major
oncogenic
driver
in
pancreatic
ductal
adenocarcinoma
(PDAC).
A
small
subset
of
PDACs
harbor
wild-type
(WT).
We
aim
to
characterize
the
molecular
profiles
WT
PDAC
uncover
new
pathogenic
drivers
and
offer
targeted
treatments.