Immunogenic cell stress and death
Nature Immunology,
Год журнала:
2022,
Номер
23(4), С. 487 - 500
Опубликована: Фев. 10, 2022
Язык: Английский
Mitochondrial control of inflammation
Nature reviews. Immunology,
Год журнала:
2022,
Номер
23(3), С. 159 - 173
Опубликована: Июль 25, 2022
Язык: Английский
Dendritic cell subsets in cancer immunity and tumor antigen sensing
Cellular and Molecular Immunology,
Год журнала:
2023,
Номер
20(5), С. 432 - 447
Опубликована: Март 22, 2023
Abstract
Dendritic
cells
(DCs)
exhibit
a
specialized
antigen-presenting
function
and
play
crucial
roles
in
both
innate
adaptive
immune
responses.
Due
to
their
ability
cross-present
tumor
cell-associated
antigens
naïve
T
cells,
DCs
are
instrumental
the
generation
of
specific
T-cell-mediated
antitumor
effector
responses
control
growth
cell
dissemination.
Within
an
immunosuppressive
microenvironment,
DC
functions
can,
however,
be
severely
impaired.
In
this
review,
we
focus
on
mechanisms
capture
activation
by
role
microenvironment
shaping
functions,
taking
advantage
recent
studies
showing
phenotype
acquisition,
transcriptional
state
functional
programs
revealed
scRNA-seq
analysis.
The
therapeutic
potential
DC-mediated
antigen
sensing
priming
immunity
is
also
discussed.
Язык: Английский
Cancer evolution: Darwin and beyond
The EMBO Journal,
Год журнала:
2021,
Номер
40(18)
Опубликована: Авг. 30, 2021
Review30
August
2021Open
Access
Cancer
evolution:
Darwin
and
beyond
Roberto
Vendramin
orcid.org/0000-0001-7191-4887
Research
UK
Lung
Centre
of
Excellence,
University
College
London
Institute,
London,
Search
for
more
papers
by
this
author
Kevin
Litchfield
Corresponding
Author
[email
protected]
Charles
Swanton
Evolution
Genome
Instability
Laboratory,
The
Francis
Crick
Information
Vendramin1,
*,1
*,1,2
1Cancer
2Cancer
*Corresponding
author.
Tel:
+44
207679
6500;
E-mail:
203796
2047;
EMBO
Journal
(2021)40:e108389https://doi.org/10.15252/embj.2021108389
This
article
is
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2021
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Abstract
Clinical
laboratory
studies
over
recent
decades
have
established
branched
evolution
as
a
feature
cancer.
However,
while
grounded
in
somatic
selection,
several
lines
evidence
suggest
Darwinian
model
alone
insufficient
fully
explain
cancer
evolution.
First,
role
macroevolutionary
events
tumour
initiation
progression
contradicts
Darwin's
central
thesis
gradualism.
Whole-genome
doubling,
chromosomal
chromoplexy
chromothripsis
represent
examples
single
catastrophic
which
can
drive
Second,
neutral
play
some
tumours,
indicating
that
selection
not
always
driving
Third,
increasing
appreciation
ageing
soma
has
led
generalised
theories
age-dependent
carcinogenesis.
Here,
we
review
these
concepts
others,
collectively
argue
extends
Darwin.
We
also
highlight
clinical
opportunities
be
grasped
through
targeting
vulnerabilities
arising
from
non-Darwinian
patterns
Introduction
In
his
revolutionary
work
(Darwin,
1859),
provided
an
evolutionary
framework
enabled
understanding
diversification
extinction
application
three
key
concepts:
variation,
heredity
selection.
More
than
100
years
later,
observation
heterogeneity
advanced
malignancies
Peter
Nowell
hypothesise
tumorigenesis
process,
whereby
same
principles
could
applied
elucidate
mechanisms
responsible
formation
development
(Nowell,
1976).
Owing
Nowell's
seminal
work,
been
historically
adopted
develop
models
therapy
resistance
(Michor
et
al,
2004;
Gatenby
Vincent,
2008;
Pepper
2009;
Greaves
Maley,
2012)
(see
Box
1).
While
gene-centric
shown
trajectories
multiple
instances
(Gerlinger
Swanton,
2010;
Purushotham
Sullivan,
Gillies
2012),
suggested
additional
are
required
reconcile
full
spectrum
behaviours
Specifically,
now
supports
jumps
(Stephens
2011;
Baca
2013;
Sottoriva
2015),
likely
interspaced
phases
microevolutionary
Furthermore,
discordant
inheritance
between
cells
(Decarvalho
2018),
(Ling
2015;
Williams
2016;
Wu
2016),
cell
plasticity
(Pogrebniak
Curtis,
2018;
Mills
2019;
Boumahdi
de
Sauvage,
2020)
microenvironment
(Coussens
Werb,
2002;
Lin
Karin,
2007;
Laconi
demand
consideration
broader
set
models.
Understanding
how
influences
disease
such
processes
shaped
environmental
factors
treatment
remains
critical.
With
review,
discuss
our
process
but
light
data,
must
incorporate
into
larger
conceptual
inclusive
alternative
approaches
understand,
predict
better
respond
improve
patient
outcome.
basis
subclonal
diversity
viewed
perspective
(Greaves
2012).
Indeed,
tumours
frequently
typified
large
population
genetically
diverse
giving
rise
distinct
subpopulations.
Subclones
will
compete
with
one
another
limited
nutrients
metabolites
face
ever-shifting
selective
pressures
driven
both
endogenous
(i.e.
microenvironmental
geographical
barriers)
exogenous
therapy)
(Merlo
2006).
outcome
competition
survival
clones
adapted
grow
under
very
specific
conditions,
highly
contextual
blind
future.
Many
were
dominant
at
point
time
may
reach
dead
ends
disappear,
only
minority
able
persist.
Quoting
"One
general
law,
leading
advancement
all
organic
beings,
namely,
multiply,
vary,
let
strongest
live
weakest
die"
1859).
two
decades,
direct
support
reported,
principally
using
next-generation
sequencing
(NGS)
perform
detailed
characterisation
genetic
2).
One
earliest
was
Shah
al
(2009),
where
matched
primary
metastatic
tissue
lobular
breast
sequenced
revealing
extensive
mutational
∼80%
non-synonymous
mutations
metastasis
absent
site
(Shah
2009).
finding
pervasive
additionally
reported
Kornelia
Polyak,
demonstrated
composed
variety
types
morphologies
behaviours,
source
clonal
(Campbell
2007).
Early
abundant,
subpopulations
revealed
single-cell
2)
Nick
Navin
others
(Navin
2011).
Regarding
haematological
malignancies,
Anderson
al.
among
first
show
branching
acute
lymphoblastic
leukaemia
(Anderson
Our
own
Gerlinger
(2012)
profiled
30
samples
four
renal
carcinoma
patients
63
69%
detectable
across
every
region
These
observations
extent
relevance
parallel
suppressor
genes
(SETD2,
PTEN,
KDM5C),
suggesting
inactivation
gene
times
within
tumour.
report
followed
Nik-Zainal
(2012b),
who
studied
life
history
21
identifying
variation
individual
(Nik-Zainal
2012b).
study
showed
further
each
containing
lineage,
representing
50%
cells.
Extending
detail
on
Gundem
(2015)
utilised
autopsy
sampling
10
prostate
identify
seeding
common
event
(Gundem
2015).
emphasised
diversification,
complexity
routes
sites.
early
small
sample
sizes.
range
meant
nature
patterns,
generalisable
or
histology
specific,
remained
undetermined.
Despite
limitations,
NGS
gave
hence
supporting
growth
(Fig
demonstration
solid
spurred
change
thinking
community
recognise
importance
Branched
applicable
relatively
homogeneous
and/or
metastases,
particularly
aggressive
subclones
achieve
sweep
present
clinically
profile
(Reiter
2018)
Clear
described
pancreatic
cancer,
virtually
major
driver
alterations
(KRAS,
CDKN2A,
TP53,
SMAD4)
most
ancestor
observed
metastases
(Makohon-Moore
2017).
Similar
carcinomas,
∼10–20%
exhibit
mutations,
poor
(Turajlic
2018).
It
proposed
reflect
differences
inherent
biology
given
impact
upon
dissemination
(Iacobuzio-Donahue
2020).
Figure
1.
Models
linear
(A),
(B),
macroevolution
(C)
(D)
Muller
plots
dynamic
changes
size
(left),
lineages
phylogenetic
trees
(centre)
number
(right).
Colours
indicate
different
clones.
Download
figure
PowerPoint
accumulating
subject
pressure
sufficient
histories,
points
existence
important
features
Macroevolution
punctuated
Neo-Darwinian
generally
assume
acquired
sequentially
gradual
fashion
time.
cases,
genomic
aberrations
occur
short
bursts
2013),
consequence
instability
(CIN)
(Bakhoum
Landau,
2017),
breakage-fusion-bridge
(BFB)
cycles
(Gisselsson
2000),
(Baca
Notta
2016)
other
similar
According
model,
alternate
long
relative
equilibrium
periods
intense
evolution,
acquire
strong
(Cross
Such
saltatory
that,
least
certain
circumstances
make
jumps,
contrary
what
predicted.
reminiscent
"hopeful
monsters"
theorised
Richard
Goldschmidt,
i.e.
organisms
profound
mutant
genotype
compared
their
parents
hold
potential
establish
novel
lineage
(Goldschmidt,
1941).
Hence,
change,
potentially
obtain
greater
fitness
would
possible
accumulation
alterations,
owing
simultaneous
acquisition
(Korbel
Campbell,
2013).
phenotypic
hereditary
if
any
all,
often
deleterious
rare
it
result
increase
cellular
generation
viable
1941;
2014b).
2.
Scales
Schematic
illustration
determinants
influence
interdependent
mechanisms,
microscopic
(left)
macroscopic
(right)
scale.
death,
implicates
drivers
progression.
For
example,
prospective
TRACERx
(TRAcking
(Rx))
(Jamal-Hanjani
elevated
copy
identified
being
strongly
associated
recurrence/death
risk
non-small
lung
(NSCLC),
whereas
nucleotide
variant
non-significant.
Similarly,
aneuploidy
detected
recurrent
gliomas
(Barthel
2019),
alongside
(characterised
high
weighted
genome
integrity
index
(Endesfelder
2014))
emerged
significant
determinant
clear
(ccRCC)
ccRCC,
losses
chromosomes
9p21.3
(CDKN2A)
14q31.1
(HIF1A)
specifically
reduced
prognostic
form
(SCNAs),
above
becoming
increasingly
recognised
pan-cancer
phenomenon
(Smith
Sheltzer,
A
outstanding
challenge
however
minimal
mapping
SCNA
cytobands,
find
causative
genes.
And
even
when
emerge,
case
CDKN2A
9p21
functional
delineate
precise
completed.
Additional
occurring
few
cataclysmic
events,
termed
chromoplexy,
ER/PR/HER2
negative
cancers
found
undergo
remain
stable
later
stages
(Gao
2016).
Tumour
chromothripsis,
thought
complex
rearrangements
involving
dozens
breakpoints
types,
bone
2011),
colon
(Kloosterman
neuroblastoma
(Molenaar
glioblastoma
(Malhotra
2013)
(Notta
An
extreme
caused
aforementioned
"big
bang"
crises
tumourigenesis
numerous
intermixed
substantially
evolve
due
weak
(Sottoriva
dynamics
cancers,
including
2015)
hepatocellular
well
conceptually
asexually
reproducing
organisms,
terms
cannot
mitigated
sexual
reproduction.
mechanism
alleviate
irreversible
detrimental
(e.g.
LOH
events)
whole
doubling
(WGD),
prevalent
(Storchova
Pellman,
Zack
Dewhurst
2014;
Bielski
entire
genome.
presence
additional,
doubled
wild-type
alleles
WGD
allow
tolerate
essential
(López
occurrence
therefore
creates
tolerant
permissive
environment
fuel
rapid
CIN,
facilitate
sub
functionalisation
duplicated
Huminiecki
Conant,
2012;
2014).
Consequently,
rates
(Zack
2014)
prognosis
intrinsic
drug
(McGranahan
Importantly,
classes
trigger
events.
instance,
prone
arise
genomically
unstable
cells,
those
harbouring
damaged
telomeres
hyperploidy
(Mardin
BFB
generate
amounts
providing
free
DNA
engage
rearrangement
compromising
centromere
function
(Umbreit
replication
stress
promoting
structural
numerical
(Burrell
triggering
nucleotide-level
mutagenesis
mediated
via
APOBEC3B
induction
(Kanu
turn
leads
incomplete
(Venkatesan
2021).
Relatedly,
regional
clusters
(kataegis)
2011)
lesion
segregation
(Aitken
architectures
2012a).
combination
rapidly
accelerates
causing
non-gradualism
class
itself
would.
Discordant
Recent
oncogene
amplification
extrachromosomal
(ecDNA)
frequent
(Verhaak
2019).
material
outside
autosomal
recognised,
reports
oncogenic
ecDNAs
going
back
far
1980s,
sequences
resembling
MYCN
(Kohl
1983).
last
frequency
started
appreciated,
thanks
techniques
long-read
whole-genome
circular
library
enrichment
structures
located
variable
(ranging
168
kb
5
Mb,
median
1.26
Mb)
(Wu
contain
oncogenes
(Bailey
provide
maintain
potent
expression
open
chromatin,
allows
increased
encoded
counterparts
Kim
defies
Mendelian
genetics.
replicated
during
S
phase,
but,
lack
centromeres,
they
unequal
randomly
inherited
daughter
mitosis.
As
such,
ecDNA-based
accelerate
non-Mendelian
expansion
backgrounds
random
distribution
fosters
cell-to-cell
variability
transcriptional
levels
oncogenes,
enabling
ITH
efficiently
amplifications
(Turner
2017;
Verhaak
Several
ecDNA
(albeit
numbers)
lung,
(Fan
Turner
Deshpande
Bailey
2020;
Koche
Key
MYC,
MYCN,
EGFR,
PDGFRA,
MET,
HER2,
DHFR,
CDK4
MDM2
ecDNAs,
ecDNA-mediated
Gu
proliferation,
invasion
metastatisation
negatively
correlate
overall
elimination
decrease
affect
(Shimizu
1998;
Nathanson
Clarke
Oobatake
Shimizu,
enable
adaptation
response
conditions
Decarvalho
2020),
though
represents
cancer-specific
vulnerability
(Nathanson
Neutral
based
Motoo
Kimura's
genetics
postulated
vast
majority
molecular
rather
fixation
selectively
drift
(Kimura,
cancer-driving
selected
accumulate
prior
initiation,
carcinogenic
insults.
Those
development,
little
no
contribution
course
Therefore,
entirely
(nearly)
study,
multi-region
>
300
regions
indicated
there
particular
clone
allele
frequencies
TCGA
cohorts
used
conclude
up
one-third
do
indications
(Williams
results
overestimation
low
resolution
data
suffer
bias
modelling,
since
abundance
distributions
enough
information
exclude
(Tarabichi
Bozic
theory
essentially
states
neutral,
especially
sizes
purifying
Most
variants
effect,
ones
predominantly
deleterious,
predicted
mathematical
modelling
(Cannataro
Kimura
never
excluded
occasional
positive
applying
changes,
metastatisation,
therapeutic
intervention)
taken
consideration.
treatment-naïve
its
progression,
emergence
forces,
pressure,
still
previously
(Almendro
worth
noting
non-cell-autonomous
give
false
impression
(Marusyk
Polyak's
group
subclone
does
higher
fitness,
instead
stimulates
scenario,
misleading
absence
predominant
relevant
frames
simultaneously
fuelling
Non-genetic
There
non-genetic—often
non-heritable—determinants,
(TME)
(Caiado
Ramón
y
Cajal
Cell
notion
dynamically
switch
state
stresses
without
gaining
recognition
(discussed
reviews
series
Milan
phenomenon,
plasticity,
characterised
fundamental
biological
properties
reversible
epigenetic
(in
sharp
contrast
binary
largely
effects)
(Calabrese
advantages
ability
swiftly
react
finely
tuned
graded
adaptive
responses
stressors
inflammation
(Rambow
classic
example
epithelial–mesenchymal
transition
(EMT)
(Nieto
(extensively
covered
Brabletz
(2021)
series).
genome,
plethora
phenotypes,
promoted
intervention
(Kemper
Gunnarsson
Marine
extensively
escape
pressure.
identification
drug-tolerant
persisters
(DTPs)
emerging
drug-sensitive
NSCLC
exposure
EGFR
tyrosine
kinase
inhibitor
(Sharma
2010).
phenotype
transiently
lost
thereby
demonstrating
reversibly
non-genetic
switch.
phenotypically
distinct—yet
interdependent—drug-tolerant
populations
recently
emerge
melanoma
PDX
MAPKi
although
resistant
phenotypes
non-heritable,
protect
eradication
permanent
melanoma,
initially
transient
converted
stably
(Shaffer
healthy
tissues
display
genes,
suggests
malignant
transformation
(Martincorena
2015,
Teixeira
Yizhak
Yoshida
noted
t
Язык: Английский
ATP and cancer immunosurveillance
The EMBO Journal,
Год журнала:
2021,
Номер
40(13)
Опубликована: Июнь 14, 2021
Язык: Английский
CD39/CD73/A2AR pathway and cancer immunotherapy
Molecular Cancer,
Год журнала:
2023,
Номер
22(1)
Опубликована: Март 2, 2023
Abstract
Cancer
development
is
closely
associated
with
immunosuppressive
tumor
microenvironment
(TME)
that
attenuates
antitumor
immune
responses
and
promotes
cell
immunologic
escape.
The
sequential
conversion
of
extracellular
ATP
into
adenosine
by
two
important
cell-surface
ectonucleosidases
CD39
CD73
play
critical
roles
in
reshaping
an
TME.
accumulated
mediates
its
regulatory
functions
binding
to
one
four
receptors
(A1R,
A2AR,
A2BR
A3R).
A2AR
elicits
profound
function
via
regulating
cAMP
signaling.
increasing
evidence
suggests
CD39,
could
be
used
as
novel
therapeutic
targets
for
manipulating
the
immunity.
In
recent
years,
monoclonal
antibodies
or
small
molecule
inhibitors
targeting
CD39/CD73/A2AR
pathway
have
been
investigated
clinical
trials
single
agents
combination
anti-PD-1/PD-L1
therapies.
this
review,
we
provide
updated
summary
about
pathophysiological
adenosinergic
cancer
development,
metastasis
drug
resistance.
more
components
therapy
circumvention
immunotherapy
resistance
are
also
discussed.
Emerging
biomarkers
may
guide
selection
CD39/CD73/A2AR-targeting
treatment
strategies
individual
patients
deliberated.
Язык: Английский
The multifaceted role of autophagy in cancer
The EMBO Journal,
Год журнала:
2022,
Номер
41(13)
Опубликована: Май 10, 2022
Язык: Английский
Cell death, therapeutics, and the immune response in cancer
Trends in cancer,
Год журнала:
2023,
Номер
9(5), С. 381 - 396
Опубликована: Фев. 24, 2023
Язык: Английский
Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy
Journal of Hematology & Oncology,
Год журнала:
2022,
Номер
15(1)
Опубликована: Апрель 27, 2022
Abstract
Targeting
nucleotide
metabolism
can
not
only
inhibit
tumor
initiation
and
progression
but
also
exert
serious
side
effects.
With
in-depth
studies
of
metabolism,
our
understanding
in
tumors
has
revealed
their
non-proliferative
effects
on
immune
escape,
indicating
the
potential
effectiveness
antimetabolites
for
enhancing
immunotherapy.
A
growing
body
evidence
now
supports
concept
that
targeting
increase
antitumor
response
by
(1)
activating
host
systems
via
maintaining
concentrations
several
important
metabolites,
such
as
adenosine
ATP,
(2)
promoting
immunogenicity
caused
increased
mutability
genomic
instability
disrupting
purine
pyrimidine
pool,
(3)
releasing
nucleoside
analogs
microbes
to
regulate
immunity.
Therapeutic
approaches
combined
with
immunotherapy
have
achieved
exciting
success
preclinical
animal
models.
Here,
we
review
how
dysregulated
promote
growth
interact
system,
provide
future
insights
into
immunotherapeutic
treatment
various
malignancies.
Язык: Английский
Targeting immunogenic cell stress and death for cancer therapy
Nature Reviews Drug Discovery,
Год журнала:
2024,
Номер
23(6), С. 445 - 460
Опубликована: Апрель 15, 2024
Язык: Английский
