CD30 ligand in lymphoma patients with CD30⁺ tumors

Purpose: 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. Materials and 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. Conclusion: 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.