Immune Response Induced in Small-Cell Lung Cancer by Maintenance Therapy With Interferon

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Abstract
Background : Chemotherapy, with or without radiotherapy, results in a 30%–40% complete response rate in small-cell lung cancer (SCLC), but approximately 90% of patients who have complete remission die within 2 years after relapse with chemoresistant disease. Randomized clinical studies of maintenance chemotherapy after complete response have failed to demonstrate survival advantage. However, studies have shown that the human cytokine interferon γ (IFN-γ) induces immune response in humans, including T-cell activation and expression of class II major histocompatibility complex (HLA-DR) and receptor for the Fc portion of immunoglobulin on monocytes. It has also been demonstrated that recombinant IFN-γ (rIFN-γ) induces immunomodulation and has antiproliferative activity. Purpose : In vivo effects of rIFN-γ treatment were characterized by flow cytometric analysis of peripheral blood mononuclear cells in patients with SCLC who received rIFN-γ; as maintenance treatment. Methods : After induction chemotherapy and radiotherapy, 100 patients who achieved a complete remission were randomly assigned to receive rIFN-γ; at a dose of 0.2 mg (4 × 10 6 units) once a day, subcutaneously, for 6 months, or observation only. In 31 patients, peripheral mononuclear cells were obtained prior to the study and at weeks 4, 8, and 12 for serial monitoring of immune response. By flow cytometric analysis, we identified the lymphocyte and monocyte populations using characteristic differences in electronic volume and right-angle scatter. In these populations, we determined the mean fluorescence channel after staining for CD14 (antigen expressed on monocytes), CD3 (antigen expressed on T lymphocytes), and HLA-DR (HLA class II expressed by monocytes and activated lymphocytes). To determine the number of Fc receptors per cell, an Fc receptor assay was performed using the monocyte cell line U937 as a standard. Results : At weeks, 4, 8, and 12, expression of HLA-DR and Fc receptors on monocytes in patients who received rIFN-γ; was significantly higher than that in untreated patients, and the difference was statistically significant. The number of Fc receptors per monocyte consistently increased during the rIFN-γ; treatment and reached a fivefold elevation at week 12. There was no statistically significant difference in lymphocyte surface antigen expression between the treated and untreated groups. Conclusion : The dose of rIFN-γ; used in this study resulted in immune stimulation in patients with SCLC who had complete remission after induction therapy. The in vivo immuno-modulatory activity of rIFN-γ; in such patients is characterized by a strong monocyte activation but no significant alteration in T-cell activation. [J Natl Cancer Inst 85:1844–1850, 1993]

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