Knockout IL4I1 affects macrophages to improve poor efficacy of CD19 CAR-T combined with PD-1 inhibitor in relapsed/refractory diffuse large B-cell lymphoma
Abstract
Chimeric
antigen
receptor
(CAR)
T-cell
therapy
plays
a
critical
role
in
the
treatment
of
B-cell
hematologic
malignancies.
The
combination
PD-1
inhibitors
and
CAR-T
has
shown
encouraging
results
treating
patients
with
relapsed/refractory
(R/R)
diffuse
large
lymphoma
(DLBCL).
However,
there
are
still
cases
where
is
ineffective.
This
study
aimed
to
investigate
IL4I1
poor
efficacy
CD19
combined
R/R
DLBCL
explore
potential
mechanisms.
Transcriptomic
metabolomic
correlation
analyses
were
performed
on
tumor
tissue
from
patients.
We
employed
an
vitro
co-culture
system
consisting
Pfeiffer
cells,
macrophages
underlying
It
was
found
that
levels
significantly
increased
tissues
compared
responders.
Correlation
analysis
revealed
positive
association
between
tryptophan
(Trp)-kynurenic
acid
(Kyn)
related
metabolites.
In
model,
presence
inhibited
cytotoxicity
cells.
Depletion
disrupted
IDO-AHR-Kyn
signaling
pathway,
thereby
enhancing
effectiveness
for
treatment.
CAR-T-mediated
when
present
model.
These
findings
suggest
may
be
contributing
factor
prognosis
expression
enhances
immunosuppression
via
inhibiting
CAR-T.
Therefore,
suppression
represent
target
DLBCL.
Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 25, 2024
Language: Английский