CD30 LIGAND IN LYMPHOMA PATIENTS WITH CD30(+) TUMORS

Purpose: CD30 ligand (CD30L), which is expressed on resting B and acti vated T lymphocytes, can induce cell death in several CD30(+) cell lin es, Patients with CD30(+) tumors (Hodgkin's disease and Ki-1(+) non-Ho dgkin's lymphoma) frequently have elevated soluble CD30 (sCD30) levels in their serum, which correlates with a poor prognosis. The role of s CD30 in protecting tumor cells from CD30L-mediated cell death and the pattern of CD30L expression on human peripheral-blood lymphocytes (PBL s) of normal donors and patients with CD30(+) tumors are investigated, Materials and Methods: CD30L surface protein expression was determine d by two-color flow cytometry on PBLs of patients with CD30(+) tumors and normal individuals. CD30L levels were determined on subsets of PBL s 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 tes ted in a CD30(+) cell line by the annexin V-binding method. Results: U nstimulated T lymphocytes of normal donors and patients with lymphoma rarely expressed CD30L surface protein, but were able to express it af ter stimulation with PHA or anti-CD3 antibody. Resting B cells of pati ents with CD30(+) tumors had lower levels of detectable surface CD30L compared with normal donors (mean, 55% and 80.6%, respectively; P = .0 008). Patients with high levels of serum sCD30 had lower detectable le vels of CD30L on their PBLs (R-2 = .72, P = .0008) and exogenous sCD30 blocked membrane-bound CD30L-mediated apoptosis in a CD30(+) cell lin e. Conclusion: In patients with CD30(+) tumors, sCD30 can decrease the availability of CD30L on PBLs. Blocking the apoptosis-inducing activi ty of CD30L by its soluble receptor may explain how CD30(+) tumors esc ape immunosurveillance and may be related to the reported poor prognos is of patients who have elevated sCD30 levels. (C) 1997 by American So ciety of Clinical Oncology.