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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
"b-cell lymphoma"
symptom
adrenal incidentaloma
alpha-thalassemia
esophageal carcinoma
hodgkin lymphoma, classical
primary effusion lymphoma
severe combined immunodeficiency
systemic capillary leak syndrome
waldenström macroglobulinemia
wiskott-aldrich syndrome
This symptom has already been validated