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Low GILT Expression is Associated with Poor Patient Survival in Diffuse Large B-Cell Lymphoma.
[hodgkin lymphoma, classical]
The
major
histocompatibility
complex
(
MHC
)
class
II
-
restricted
antigen
processing
pathway
presents
antigenic
peptides
acquired
in
the
endocytic
route
for
the
activation
of
CD
4
(
+
)
T
cells
.
Multiple
cancers
express
MHC
class
II
,
which
may
influence
the
anti-
tumor
immune
response
and
patient
outcome
.
Low
MHC
class
II
expression
is
associated
with
poor
survival
in
diffuse
large
B-
cell
lymphoma
(
DLBCL
)
,
the
most
common
form
of
aggressive
non-
Hodgkin
lymphoma
.
Therefore
,
we
investigated
whether
gamma-interferon-inducible
lysosomal
thiol
reductase
(
GILT
)
,
an
upstream
component
of
the
MHC
class
II
-
restricted
antigen
processing
pathway
that
is
not
regulated
by
the
transcription
factor
class
II
transactivator
,
may
be
important
in
DLBCL
biology
.
GILT
reduces
protein
disulfide
bonds
in
the
endocytic
compartment
,
exposing
additional
epitopes
for
binding
to
MHC
class
II
and
facilitating
antigen
presentation
.
In
each
of
four
independent
gene
expression
profiling
cohorts
with
a
total
of
585
DLBCL
patients
,
low
GILT
expression
was
significantly
associated
with
poor
overall
survival
.
In
contrast
,
low
expression
of
a
classical
MHC
class
II
gene
,
HLA-DRA
,
was
associated
with
poor
survival
in
one
of
four
cohorts
.
The
association
of
low
GILT
expression
with
poor
survival
was
independent
of
established
clinical
and
molecular
prognostic
factors
,
the
International
Prognostic
Index
and
the
cell
of
origin
classification
,
respectively
.
Immunohistochemical
analysis
of
GILT
expression
in
96
DLBCL
cases
demonstrated
variation
in
GILT
protein
expression
within
tumor
cells
which
correlated
strongly
with
GILT
mRNA
expression
.
These
studies
identify
a
novel
association
between
GILT
expression
and
clinical
outcome
in
lymphoma
.
Our
findings
underscore
the
role
of
antigen
processing
in
DLBCL
and
suggest
that
molecules
targeting
this
pathway
warrant
investigation
as
potential
therapeutics
.
Diseases
Validation
Diseases presenting
"tumor cells"
symptom
alpha-thalassemia
carcinoma of the gallbladder
cholangiocarcinoma
cushing syndrome
dedifferentiated liposarcoma
dentin dysplasia
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
junctional epidermolysis bullosa
kindler syndrome
liposarcoma
lymphangioleiomyomatosis
pleomorphic liposarcoma
primary effusion lymphoma
severe combined immunodeficiency
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
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