Science Advances,
Journal Year:
2023,
Volume and Issue:
9(7)
Published: Feb. 15, 2023
T
cell
engineering
has
changed
the
landscape
of
cancer
immunotherapy.
Chimeric
antigen
receptor
cells
have
demonstrated
a
remarkable
efficacy
in
treatment
B
malignancies
hematology.
However,
their
clinical
impact
on
solid
tumors
been
modest
so
far.
expressing
an
engineered
(TCR-T
cells)
represent
promising
therapeutic
alternative.
The
target
repertoire
is
not
limited
to
membrane
proteins,
and
intrinsic
features
TCRs
such
as
high
sensitivity
near-to-physiological
signaling
may
improve
tumor
detection
killing
while
improving
persistence.
In
this
review,
we
present
results
obtained
with
TCR-T
targeting
different
families.
We
detail
methods
that
developed
identify
optimize
TCR
candidate.
also
discuss
challenges
therapies,
including
toxicity
assessment
resistance
mechanisms.
Last,
share
some
perspectives
highlight
future
directions
field.
Annual Review of Immunology,
Journal Year:
2018,
Volume and Issue:
36(1), P. 639 - 665
Published: Feb. 5, 2018
Granulomas
are
organized
aggregates
of
macrophages,
often
with
characteristic
morphological
changes,
and
other
immune
cells.
These
evolutionarily
ancient
structures
form
in
response
to
persistent
particulate
stimuli-infectious
or
noninfectious-that
individual
macrophages
cannot
eradicate.
evolved
as
protective
responses
destroy
sequester
particles
but
frequently
pathological
the
context
foreign
bodies,
infections,
inflammatory
diseases.
We
summarize
recent
findings
that
suggest
granulomatous
unfolds
a
stepwise
program
characterized
by
series
macrophage
activations
transformations
turn
recruit
additional
cells
produce
structural
changes.
explore
why
different
granulomas
vary
reasons
pathogenic.
Understanding
mechanisms
role
granuloma
formation
may
uncover
new
therapies
for
multitude
diseases
constitute
serious
medical
problems
while
enhancing
function
infections.
Cancer Research,
Journal Year:
2018,
Volume and Issue:
79(6), P. 1214 - 1225
Published: Dec. 12, 2018
Abstract
Despite
the
initial
successes
of
immunotherapy,
there
is
an
urgent
clinical
need
for
molecular
assays
that
identify
patients
more
likely
to
respond.
Here,
we
report
ultrasensitive
measures
circulating
tumor
DNA
(ctDNA)
and
T-cell
expansion
can
be
used
assess
responses
immune
checkpoint
blockade
in
metastatic
lung
cancer
(N
=
24).
Patients
with
response
therapy
had
a
complete
reduction
ctDNA
levels
after
initiation
therapy,
whereas
nonresponders
no
significant
changes
or
increase
levels.
followed
by
acquired
resistance
drop
recrudescence
without
shorter
progression-free
overall
survival
compared
responders
[5.2
vs.
14.5
8.4
18.7
months;
HR
5.36;
95%
confidence
interval
(CI),
1.57–18.35;
P
0.007
6.91;
CI,
1.37–34.97;
0.02,
respectively],
which
was
detected
on
average
8.7
weeks
earlier
predictive
benefit
than
CT
imaging.
Expansion
T
cells,
measured
through
increases
receptor
productive
frequencies,
mirrored
therapy.
We
validated
this
approach
independent
cohort
early-stage
non–small
cell
14),
where
therapeutic
effect
pathologic
assessment
residual
anti-PD1
Consistent
our
findings,
early
dynamics
predicted
blockade.
These
analyses
provide
rapid
determination
outcomes
treated
inhibitors
have
important
implications
development
personalized
targeted
strategies.
Significance:
Rapid
sensitive
detection
dynamic
guide
cancer.
See
related
commentary
Zou
Meyerson,
p.
1038
Cell,
Journal Year:
2017,
Volume and Issue:
172(3), P. 549 - 563.e16
Published: Dec. 21, 2017
Highlights•Development
of
a
human
leukocyte
antigen
library
for
TCR
ligand
identification•Single-cell
sequencing
and
phenotyping
T
cells
infiltrating
colon
cancer•Ligand
discovery
four
tumor-derived
cell
receptors•Identification
shared
non-mutated
tumor
between
two
patientsSummaryThe
immune
system
can
mount
responses
against
tumors;
however,
the
specificities
tumor-infiltrating
lymphocytes
(TILs)
are
not
well
understood.
We
used
yeast-display
libraries
peptide-human
(pHLA)
to
screen
antigens
"orphan"
receptors
(TCRs)
expressed
on
TILs
from
colorectal
adenocarcinoma.
Four
TIL-derived
TCRs
exhibited
strong
selection
peptides
presented
in
highly
diverse
pHLA-A∗02:01
library.
Three
TIL
were
specific
self-antigens,
which
present
separate
patient
tumors,
specificity
self-antigen
derived
U2AF2.
These
results
show
that
exposed
recognition
surface
MHC-bound
accessible
contains
sufficient
structural
information
enable
reconstruction
sequences
peptide
targets
pathogenic
unknown
specificity.
This
finding
underscores
surprising
their
cognate
enables
facile
indentification
through
unbiased
screening.Graphical
abstract
Annual Review of Immunology,
Journal Year:
2018,
Volume and Issue:
36(1), P. 359 - 381
Published: Feb. 5, 2018
IgA
is
the
dominant
immunoglobulin
isotype
produced
in
mammals,
largely
secreted
across
intestinal
mucosal
surface.
Although
induction
of
has
been
a
hallmark
feature
microbiota
colonization
following
germ-free
animals,
until
recently
appreciation
function
host-microbial
mutualism
depended
mainly
on
indirect
evidence
alterations
composition
or
penetration
microbes
absence
somatic
mutations
(or
compensatory
IgM).
Highly
parallel
sequencing
techniques
that
enable
high-resolution
analysis
either
microbial
consortia
sequence
diversity
are
now
giving
us
new
perspectives
selective
targeting
taxa
and
trajectory
diversification
according
to
mechanisms,
between
different
individuals
over
time.
The
prospects
link
range
diversified
clonotypes
specific
antigenic
functions
modulating
composition,
position
metabolism
ensure
host
mutualism.
