Correlation between the biological and therapeutic effects of interferon-alpha in low-grade nodular non-Hodgkin's lymphoma: Lack of in vivo down-regulation and reduced affinity of IFN-α receptors in unresponsive patients

• Published in: Leukemia research Vol. 15; no. 2; pp. 121 - 128
• Main Authors: Billard, C., Ferbus, D., Diez, R.A., Kolb, J.P., Mathiot, C., Belanger, C., Auzanneau, G., Varet, B., Falcoff, E., Dumont, J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1991; Elsevier Science
• Subjects: 2',5'-Oligoadenylate Synthetase - metabolism; 2–5A synthetase; affinity; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biological and medical sciences; Cell Division; clinical responsiveness; Down-Regulation; Drug Evaluation; Humans; IFN-α; Immunopathology; Interferon Type I - metabolism; Interferon Type I - therapeutic use; Interleukin-4 - pharmacology; Leukocytes, Mononuclear - metabolism; Lymphoma, Follicular - metabolism; Lymphoma, Follicular - pathology; Lymphoma, Follicular - therapy; Lymphoma, Non-Hodgkin - metabolism; Lymphoma, Non-Hodgkin - pathology; Lymphoma, Non-Hodgkin - therapy; Medical sciences; Nodular NHL; receptors; Receptors, Immunologic - metabolism; Receptors, Interferon; regulation; Remission Induction; Tumor Cells, Cultured - metabolism; Tumor Cells, Cultured - pathology; PBS; PR; CML; receptors; NR; 2–5A synthetase; MR; PBMC; K d; CR; IFN-α; HCL; LMW-BCGF; NHL; regulation; Nodular NHL; FCS; clinical responsiveness; affinity; Human; Malignant hemopathy; Clinical investigation; Interferon; Non Hodgkin lymphoma; Biological receptor
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/0145-2126(91)90092-8

We investigated the correlations between the biological effects of interferon-alpha (IFN-α) and clinical responsiveness in low-grade non-Hodgkin's lymphomas (NHL). In this disease, 40–50% of cases respond to IFN-α therapy. Patients with nodular NHL were selected for a phase II trial in which they were treated daily with 9 × 10 6 U of IFN-α2a. Binding experiments with [ 125I]IFN-α2a showed the presence of IFN-α receptors on tumor B-cells isolated from lymph nodes before therapy in 9 out of 10 patients. Receptor levels were not related to the subsequent clinical responses. However, no specific binding was detected in one patient who turned out to be unresponsive to IFN-α treatment. Single injections of IFN-α2a before beginning the therapeutic protocol resulted in down-regulation of IFN-α receptors without change in their affinity in peripheral blood leukocytes from only patients who subsequently resonded to therapy (4/10). In 4/5 non-responders and one patient displaying a minor response, receptor numbers did not decrease but K d values rose markedly in all six cases. These results indicate that lack of in vivo IFN-α receptor down-regulation and reduced receptor affinity, as detected before therapy, may be correlated with failure of IFN-α therapy in nodular NHL.