Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: July 16, 2024
While
most
of
the
cancer
immunotherapy
strategies
engage
adaptive
immunity,
especially
tumor-associated
T
cells,
small
fraction
responding
patients
and
types
cancers
amenable,
possibility
severe
adverse
effects
limit
its
usage.
More
effective
general
interventions
are
urgently
needed.
Recently,
a
de
facto
innate
immune
memory,
termed
‘trained
immunity’,
has
become
new
research
focal
point,
promises
to
be
powerful
tool
for
achieving
long-term
therapeutic
benefits
against
cancers.
Trained
immunity-inducing
agents
such
as
BCG
fungal
glucan
have
been
shown
able
avert
suppressive
tumor
microenvironment
(TME),
enhance
cell
responses,
eventually
lead
regression.
Here,
we
review
current
understating
trained
immunity
induction
highlight
critical
roles
emergency
granulopoiesis,
interferon
γ
tissue-specific
induction.
Preclinical
clinical
studies
that
exploited
inducers
summarized,
repurposed
from
other
fields
proposed.
We
also
outline
challenges
opportunities
in
future
immunotherapies.
envisage
more
vaccines
will
combine
with
therapies.
Annual Review of Pathology Mechanisms of Disease,
Journal Year:
2021,
Volume and Issue:
17(1), P. 425 - 457
Published: Nov. 18, 2021
Chronic
inflammation
increases
the
risk
of
several
cancers,
including
gastric,
colon,
and
hepatic
cancers.
Conversely,
tumors,
similar
to
tissue
injury,
trigger
an
inflammatory
response
coordinated
by
innate
immune
system.
Cellular
molecular
mediators
modulate
tumor
growth
directly
influencing
adaptive
response.
Depending
on
balance
cell
types
signals
within
microenvironment,
can
support
or
restrain
tumor.
Adding
complexity,
research
from
past
two
decades
has
revealed
that
cells
are
highly
heterogeneous
plastic,
with
variable
phenotypes
depending
type,
stage,
treatment.
The
field
is
now
cusp
being
able
harness
this
wealth
data
(
Nature Reviews Urology,
Journal Year:
2021,
Volume and Issue:
18(10), P. 611 - 622
Published: June 15, 2021
Bacillus
Calmette-Guérin
(BCG)
is
the
most
widely
used
vaccine
worldwide
and
has
been
to
prevent
tuberculosis
for
a
century.
BCG
also
stimulates
an
anti-tumour
immune
response,
which
urologists
have
harnessed
treatment
of
non-muscle-invasive
bladder
cancer.
A
growing
body
evidence
indicates
that
offers
protection
against
various
non-mycobacterial
viral
infections.
The
non-specific
effects
occur
via
induction
trained
immunity
form
basis
hypothesis
vaccination
could
be
protect
severity
coronavirus
disease
2019
(COVID-19).
This
Perspective
article
highlights
key
milestones
in
100-year
history
projects
its
potential
role
COVID-19
pandemic.
Periodontology 2000,
Journal Year:
2022,
Volume and Issue:
89(1), P. 166 - 180
Published: March 4, 2022
Abstract
Accumulating
evidence
demonstrates
that
the
oral
pathobiont
Fusobacterium
nucleatum
is
involved
in
progression
of
an
increasing
number
tumors
types.
Thus
far,
mechanisms
underlying
tumor
exacerbation
by
F.
include
enhancement
proliferation,
establishment
a
tumor‐promoting
immune
environment,
induction
chemoresistance,
and
activation
checkpoints.
This
review
focuses
on
mediate
tumor‐specific
colonization
fusobacteria.
Elucidating
mediating
fusobacterial
tropism
promotion
might
provide
new
insights
for
development
novel
approaches
detection
treatment.
NEJM Evidence,
Journal Year:
2022,
Volume and Issue:
2(1)
Published: Nov. 10, 2022
BackgroundPatients
with
Bacillus
Calmette–Guérin
(BCG)–unresponsive
non–muscle-invasive
bladder
cancer
(NMIBC)
have
limited
treatment
options.
The
immune
cell–activating
interleukin-15
(IL-15)
superagonist
Nogapendekin
alfa
inbakicept
(NAI),
also
known
as
N-803,
may
act
synergistically
BCG
to
elicit
durable
complete
responses
(CRs)
in
this
patient
population.MethodsIn
open-label,
multicenter
study,
patients
BCG-unresponsive
carcinoma
situ
(CIS)
or
without
Ta/T1
papillary
disease
were
treated
intravesical
NAI
plus
(cohort
A)
alone
C).
Patients
high-grade
NMIBC
received
B).
primary
end
point
was
the
incidence
of
CR
at
3-
6-month
assessment
visit
for
cohorts
A
and
C,
disease-free
survival
(DFS)
rate
12
months
cohort
B.
Durability,
cystectomy
avoidance,
progression-free
survival,
disease-specific
(DSS),
overall
secondary
points
A.ResultsIn
A,
achieved
58
(71%)
82
(95%
confidence
interval
[CI]=59.6
80.3;
median
follow-up,
23.9
months),
a
duration
26.6
CI=9.9
[upper
bound
not
reached]).
At
24
CR,
Kaplan–Meier
estimated
probability
avoiding
DSS
89.2%
100%,
respectively.
In
B
(n=72),
DFS
55.4%
CI=42.0%
66.8%)
months,
19.3
CI=7.4
Most
treatment-emergent
adverse
events
receiving
grade
1
2
(86%);
three
3
immune-related
occurred.ConclusionsIn
novel
agent
NAI,
CRs
persistence
effect,
100%
cancer–specific
months.
study
is
ongoing,
an
target
enrollment
200
participants
(Funded
by
ImmunityBio.)
Cancers,
Journal Year:
2022,
Volume and Issue:
14(13), P. 3073 - 3073
Published: June 23, 2022
BCG
is
a
live
attenuated
strain
of
Mycobacterium
bovis
that
primarily
used
as
vaccine
against
tuberculosis.
In
the
past
four
decades,
has
also
been
for
treatment
non-muscle
invasive
bladder
cancer
(NMIBC).
patients
with
NMIBC,
reduces
risk
tumor
recurrence
and
decreases
likelihood
progression
to
more
disease.
Despite
long-term
clinical
experience
BCG,
its
mechanism
action
still
being
elucidated.
Data
from
animal
models
human
studies
suggests
activates
both
innate
adaptive
arms
immune
system
eventually
leading
destruction.
Herein,
we
review
current
data
regarding
summarize
evidence
efficacy
recommended
indications
practice.
Cancer Research,
Journal Year:
2023,
Volume and Issue:
83(11), P. 1834 - 1850
Published: March 20, 2023
Abstract
N6-Methyladenosine
(m6A)
is
the
most
prevalent
internal
modification
of
mammalian
mRNAs.
Recent
studies
have
shown
that
m6A
methyltransferases
METTL3
and
METTL14
play
important
roles
in
urothelial
bladder
carcinoma
(BLCA).
To
provide
a
more
comprehensive
understanding
regulatory
landscape
cancer,
we
investigated
role
YTHDF2,
crucial
reader,
BLCA.
YTHDF2
was
frequently
upregulated
at
both
RNA
protein
level
Functionally,
promoted
proliferation
tumor
growth
BLCA
cells
vitro
vivo,
respectively.
Integrative
sequencing
analyses
identified
RIG-I
as
downstream
target
YTHDF2.
Mechanistically,
bound
to
coding
sequence
DDX58
mRNA,
which
encodes
RIG-I,
mediated
its
degradation
an
m6A-dependent
manner.
Knockdown
inhibited
apoptosis
cells.
Depleting
also
able
reverse
effects
deficiency.
YTHDF2-deficient
implanted
orthotopically
recipient
mice
activated
innate
immune
response
recruitment
CD8+
T
lymphocytes
into
bed
urothelium.
Moreover,
deficiency
enhanced
efficacy
Bacillus
Calmette-Guérin
immunotherapy
treatment.
This
study
reveals
acts
oncogene
inhibits
facilitate
evasion,
supporting
testing
inhibition
combination
with
immunotherapy.
Significance:
regulates
RIG-I–mediated
signaling
support
cancer
progression,
highlighting
functional
importance
modifications
uncovering
therapeutic
opportunities
improve
patient
outcomes.