Frontiers in Immunology,
Год журнала:
2023,
Номер
13
Опубликована: Янв. 9, 2023
Introduction
Targetable
alterations
such
as
BRAFV600E
mutation
and
NTRK
fusion
are
enriched
in
microsatellite
instability-high
(MSI-H)
colorectal
cancer
(CRC).
MSI-H
with
targetable
(MSI-H
altered)
might
present
unique
opportunities
for
both
targeted
therapy
immunotherapy.
We
systematically
evaluated
the
molecular
characteristics
immune-related
features
of
altered
without
wt)
CRC
patients
our
study.
Methods
Among
1938
continuously
enrolled
patients,
126
status
(6.50%)
were
included
this
retrospective
Genomic
transcriptomic
data
investigated
by
next-generation
sequencing
(NGS)
gene
expression
profiling
(GEP),
respectively.
Results
BRAFV600E,
NTRK1,
FGFR2
mutations
most
frequent
patients.
The
phenotype
was
significantly
associated
older
age
(p<
0.001),
right
side
(p=0.024)
females
(p=
0.036).
No
lynch
syndrome
(LS)
identified
group.
tumor
mutational
burden
(TMB),
neoantigen
(TNB)
wt
subgroups
comparable
(p<0.05).
Subsequently,
study
analysis
further
revealed
linked
to
an
immune-active
microenvironment
higher
levels
Teff
IFN-gamma,
CYT,
MERCK
18
signatures,
lower
IPRES
signature,
EMT
TGF
Beta
signatures.
In
addition,
case
supported
patient
harboring
also
achieved
a
long-term
disease-free
survival
benefit
from
Discussion
Our
preliminary
novel
subtype
signatures
microenvironment.
Given
accessibility
immune
checkpoint
inhibitors
(ICIs)
treatment,
results
provide
clinical
evidence
immunotherapy
alterations.
Journal of Hematology & Oncology,
Год журнала:
2022,
Номер
15(1)
Опубликована: Июль 16, 2022
Chemotherapy
combined
with
or
without
targeted
therapy
is
the
fundamental
treatment
for
metastatic
colorectal
cancer
(mCRC).
Due
to
adverse
effects
of
chemotherapeutic
drugs
and
biological
characteristics
tumor
cells,
it
difficult
make
breakthroughs
in
traditional
strategies.
The
immune
checkpoint
blockades
(ICB)
has
made
significant
progress
advanced
malignant
tumors,
patients
who
benefit
from
this
may
obtain
a
long-lasting
response.
Unfortunately,
immunotherapy
only
effective
limited
number
microsatellite
instability-high
(MSI-H),
segment
initial
responders
can
subsequently
develop
acquired
resistance.
From
September
4,
2014,
first
anti-PD-1/PD-L1
drug
Pembrolizumab
was
approved
by
FDA
second-line
melanoma.
Subsequently,
mCRC
2017.
Immunotherapy
rapidly
developed
past
7
years.
in-depth
research
ICB
indicated
that
mechanism
immune-resistance
become
gradually
clear,
new
predictive
biomarkers
are
constantly
emerging.
Clinical
trials
examining
effect
checkpoints
actively
carried
out,
order
produce
patients.
This
review
summarizes
strategies
patients,
discusses
application
treatment,
outlines
potential
markers
efficacy,
lists
key
results
clinical
trials,
collects
recent
basic
results,
provide
theoretical
basis
practical
direction
Advanced Materials,
Год журнала:
2023,
Номер
36(9)
Опубликована: Ноя. 8, 2023
Ferroptosis-triggered
immunogenic
cell
death
(ICD)
is
widely
adopted
to
potentiate
the
body's
antitumor
immunity
by
catalyzing
production
of
toxic
reactive
oxygen
species
(ROS).
However,
efficacy
ferroptosis
and
immunotherapy
greatly
restricted
intracellular
abundant
glutathione
(GSH)
immunosuppressive
tumor
microenvironment
(TME).
Herein,
a
facile
bottom-up
method
for
solvent-free
synthesis
ultrathin
manganese
(Mn)-based
layered
double
hydroxide
nanosheets
with
high
loading
efficiency
pro-inflammatory
cytokine
interferon
(IFNγ)
(IFNγ/uMn-LDHs)
proposed
mutually
reinforce
systemic
immunity.
The
introduction
ions
significantly
contributes
GSH
depletion
hydroxyl
radical
generation,
which
can
be
further
enhanced
IFNγ
delivery-induced
SLC7A11
downregulation.
ICD
effect
after
cooperates
intrinsic
immunomodulatory
property
IFNγ/uMn-LDHs
facilitate
maturation
dendritic
cells
(DCs)
priming
T
cells.
secretion
from
activated
CD8
Annual Review of Immunology,
Год журнала:
2024,
Номер
42(1), С. 521 - 550
Опубликована: Фев. 21, 2024
Immune
checkpoint
blockade
(ICB)
induces
a
remarkable
and
durable
response
in
subset
of
cancer
patients.
However,
most
patients
exhibit
either
primary
or
acquired
resistance
to
ICB.
This
arises
from
complex
interplay
diverse
dynamic
mechanisms
within
the
tumor
microenvironment
(TME).
These
include
genetic,
epigenetic,
metabolic
alterations
that
prevent
T
cell
trafficking
site,
induce
immune
dysfunction,
interfere
with
antigen
presentation,
drive
heightened
expression
coinhibitory
molecules,
promote
survival
after
attack.
The
TME
worsens
ICB
through
formation
immunosuppressive
networks
via
inhibition,
regulatory
metabolites,
abnormal
resource
consumption.
Finally,
patient
lifestyle
factors,
including
obesity
microbiome
composition,
influence
resistance.
Understanding
heterogeneity
cellular,
molecular,
environmental
factors
contributing
is
crucial
develop
targeted
therapeutic
interventions
enhance
clinical
response.
comprehensive
overview
highlights
key
may
be
clinically
translatable.
Journal of Hematology & Oncology,
Год журнала:
2024,
Номер
17(1)
Опубликована: Авг. 9, 2024
The
past
few
decades
have
witnessed
the
rise
of
immunotherapy
for
Gastrointestinal
(GI)
tract
cancers.
role
immune
checkpoint
inhibitors
(ICIs),
particularly
programmed
death
protein
1
(PD-1)
and
PD
ligand-1
antibodies,
has
become
increasingly
pivotal
in
treatment
advanced
perioperative
GI
Currently,
anti-PD-1
plus
chemotherapy
is
considered
as
first-line
regimen
unselected
gastric/gastroesophageal
junction
adenocarcinoma
(G/GEJC),
mismatch
repair
deficient
(dMMR)/microsatellite
instability-high
(MSI-H)
colorectal
cancer
(CRC),
esophageal
(EC).
In
addition,
encouraging
performance
claudin18.2-redirected
chimeric
antigen
receptor
T-cell
(CAR-T)
therapy
later-line
cancers
brings
new
hope
cell
solid
tumour
treatment.
Nevertheless,
remains
yet
precise,
researchers
are
dedicated
to
further
maximising
optimising
efficacy.
This
review
summarises
important
research,
latest
progress,
future
directions
including
EC,
G/GEJC,
CRC.
Cell Reports Medicine,
Год журнала:
2024,
Номер
5(5), С. 101512 - 101512
Опубликована: Апрель 18, 2024
Our
previous
work
developed
acoustic
response
bacteria,
which
enable
the
precise
tuning
of
transgene
expression
through
ultrasound.
However,
it
is
still
difficult
to
visualize
these
bacteria
in
order
guide
sound
wave
precisely
irradiate
them.
Here,
we
develop
ultrasound-visible
engineered
and
chemically
modify
them
with
doxorubicin
(DOX)
on
their
surfaces.
These
(Ec@DIG-GVs)
can
produce
gas
vesicles
(GVs),
providing
a
real-time
imaging
for
remote
hyperthermia
high-intensity
focused
ultrasound
(hHIFU)
induce
interferon
(IFN)-γ
gene.
The
production
IFN-γ
kill
tumor
cells,
macrophage
polarization
from
M2
M1
phenotype,
promote
maturation
dendritic
cells.
DOX
be
released
acidic
microenvironment,
resulting
immunogenic
cell
death
concurrent
effects
activate
tumor-specific
T
response,
producing
synergistic
anti-tumor
efficacy.
study
provides
promising
strategy
bacteria-mediated
chemo-immunotherapy.
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Сен. 9, 2022
Immunotherapies,
especially
the
programmed
cell
death
1/programmed
ligand
1
(PD-1/PD-L1)
inhibitors,
have
revolutionized
therapeutic
strategies
of
various
cancers.
As
for
colorectal
cancer
(CRC),
current
clinical
application
PD-1/PD-L1
inhibitors
are
mainly
used
according
to
mutation
pattern,
which
is
categorized
into
deficient
mismatch
repair
(dMMR)/high
levels
microsatellite
instability
(MSI-H)
and
proficient
(pMMR),
or
non-high
(non-MSI-H).
been
proven
favorable
outcomes
against
dMMR/MSI-H
CRC
because
more
T-cell
infiltration
tumor
tissues.
Nevertheless,
effectiveness
in
pMMR/non-MSI-H
still
uncertain.
Because
quite-lower
proportion
CRC,
reported
combine
with
other
antitumor
treatments
including
chemotherapy,
radiotherapy,
targeted
therapy
better
effect
recent
trials.
Neoadjuvant
therapy,
chemotherapy
not
only
can
reduce
stage
but
also
benefit
from
local
control,
improve
symptoms
quality
life.
Adding
immunotherapy
neoadjuvant
may
change
treatment
strategy
primary
resectable
some
metastatic
CRC.
In
this
review,
we
focus
on
development
anti-PD-1/PD-L1
discuss
future
perspectives
