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Reed-Sternberg cell-derived lymphotoxin-α activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma.
[hodgkin lymphoma, classical]
It
is
known
that
cells
within
the
inflammatory
background
in
classical
Hodgkin
lymphoma
(
cHL
)
provide
signals
essential
for
the
continual
survival
of
the
neoplastic
Hodgkin
and
Reed
-
Sternberg
(
HRS
)
cells
.
However
,
the
mechanisms
underlying
the
recruitment
of
this
inflammatory
infiltrate
into
the
involved
lymph
nodes
are
less
well
understood
.
In
this
study
,
we
show
in
vitro
that
HRS
cells
secrete
lymphotoxin-α
(
LT
α
)
which
acts
on
endothelial
cells
to
upregulate
the
expression
of
adhesion
molecules
that
are
important
for
T
cell
recruitment
.
LT
α
also
enhances
the
expression
of
hyaluronan
which
preferentially
contributes
to
the
recruitment
of
CD
4
(
+
)
CD
4
5
RA
(
+
)
naïve
T
cells
under
in
vitro
defined
flow
conditions
.
Enhanced
expression
of
LT
α
in
HRS
cells
and
tissue
stroma
;
and
hyaluronan
on
endothelial
cells
are
readily
detected
in
involved
lymph
nodes
from
cHL
patients
.
Our
study
also
shows
that
although
NF-κB
and
AP
-
1
are
involved
,
the
cyclooxygenase
(
COX
)
pathway
is
the
dominant
regulator
of
LT
α
production
in
HRS
cells
.
Using
pharmacological
inhibitors
,
our
data
suggest
that
activity
of
COX
1
,
but
not
of
COX
2
,
directly
regulates
the
expression
of
nuclear
c-
Fos
in
HRS
cells
.
Our
findings
suggest
that
HRS
cell-derived
LT
α
is
an
important
mediator
that
contributes
to
T
cell
recruitment
into
lesional
lymph
nodes
in
cHL
.
Diseases
Validation
Diseases presenting
"hodgkin lymphoma"
symptom
esophageal adenocarcinoma
hodgkin lymphoma, classical
monosomy 21
primary effusion lymphoma
severe combined immunodeficiency
systemic capillary leak syndrome
waldenström macroglobulinemia
This symptom has already been validated