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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
.