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-alpha receptors in unresponsive patients.
We investigated the correlations between the biological effects of interferon-alpha (IFN-alpha) and clinical responsiveness in low-grade non-Hodgkin's lymphomas (NHL). In this disease, 40-50% of cases respond to IFN-alpha therapy. Patients with nodular NHL were selected for a phase II trial in which they were treated daily with 9 x 10(6) U of IFN-alpha 2a. Binding experiments with [125I]IFN-alpha 2a showed the presence of IFN-alpha 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-alpha treatment. Single injections of IFN-alpha 2a before beginning the therapeutic protocol resulted in down-regulation of IFN-alpha receptors without change in their affinity in peripheral blood leukocytes from only patients who subsequently responded to therapy (4/10). In 4/5 non-responders and one patient displaying a minor response, receptor numbers did not decrease but Kd values rose markedly in all six cases. These results indicate that lack of in vivo IFN-alpha receptor down-regulation and reduced receptor affinity, as detected before therapy, may be correlated with failure of IFN-alpha therapy in nodular NHL.
Billard
C
C
INSERM U. 196, Institut Curie, Paris, France.
Ferbus
D
D
Diez
R A
RA
Kolb
J P
JP
Mathiot
C
C
Belanger
C
C
Auzanneau
G
G
Varet
B
B
Falcoff
E
E
Dumont
J
J
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D015536:Down-Regulation; D004341:Drug Evaluation; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011971:Receptors, Immunologic / Q000378:metabolism*; D017471:Receptors, Interferon; D012074:Remission Induction; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D007370:Interferon Type I; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D015847:Interleukin-4; D015088:2',5'-Oligoadenylate Synthetase