CD30 ligand in lymphoma patients with CD30+ tumors.
OBJECTIVE
CD30 ligand (CD30L), which is expressed on resting B and activated T lymphocytes, can induce cell death in several CD30+ cell lines. Patients with CD30+ tumors (Hodgkin's disease and Ki-1+ non-Hodgkin's lymphoma) frequently have elevated soluble CD30 (sCD30) levels in their serum, which correlates with a poor prognosis. The role of sCD30 in protecting tumor cells from CD30L-mediated cell death and the pattern of CD30L expression on human peripheral-blood lymphocytes (PBLs) of normal donors and patients with CD30+ tumors are investigated.


METHODS
CD30L surface protein expression was determined by two-color flow cytometry on PBLs of patients with CD30+ tumors and normal individuals. CD30L levels were determined on subsets of PBLs before and after stimulation with phytohemagglutinin (PHA), anti-CD3 antibody, or CD40L. sCD30 was measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic activity of membrane-bound CD30L was tested in a CD30+ cell line by the annexin V-binding method.


RESULTS
Unstimulated T lymphocytes of normal donors and patients with lymphoma rarely expressed CD30L surface protein, but were able to express it after stimulation with PHA or anti-CD3 antibody. Resting B cells of patients with CD30+ tumors had lower levels of detectable surface CD30L compared with normal donors (mean, 55% and 80.6%, respectively; P = .0008). Patients with high levels of serum sCD30 had lower detectable levels of CD30L on their PBLs (R2 = .72, P = .0008) and exogenous sCD30 blocked membrane-bound CD30L-mediated apoptosis in a CD30+ cell line.


CONCLUSIONS
In patients with CD30+ tumors, sCD30 can decrease the availability of CD30L on PBLs. Blocking the apoptosis-inducing activity of CD30L by its soluble receptor may explain how CD30+ tumors escape immunosurveillance and may be related to the reported poor prognosis of patients who have elevated sCD30 levels.
Younes
A
A
Department of Hematology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. ayounes@notes.mdacc.tmc.edu
Consoli
U
U
Snell
V
V
Clodi
K
K
Kliche
K O
KO
Palmer
J L
JL
Gruss
H J
HJ
Armitage
R
R
Thomas
E K
EK
Cabanillas
F
F
Andreeff
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D053285:CD30 Ligand; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000097:blood* / Q000473:pathology; D006801:Humans; D017730:Ki-1 Antigen / Q000097:blood*; D008024:Ligands; D008214:Lymphocytes / Q000276:immunology*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000097:blood* / Q000276:immunology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis
D053285:CD30 Ligand; D017730:Ki-1 Antigen; D008024:Ligands; D008562:Membrane Glycoproteins; C505774:TNFSF8 protein, human