Metastatic renal-cell carcinoma patients treated with interleukin 2 or interleukin 2 plus interferon gamma: immunological monitoring.
We investigated the biological response of 73 patients with metastatic renal-cell carcinoma (MRCC) treated by repetitive weekly cycles of high-dose interleukin 2 (IL-2) (protocol 1, 40 patients) or IL-2 plus interferon-gamma (IFN-gamma) (protocol 2, 33 patients). The objectives of this study were (i) to evaluate the effects of this IL-2 administration schedule on biological response, (ii) to compare the effects of IL-2 alone with those of IL-2 plus IFN-gamma, (iii) to search for any correlation between certain biological marker values and the clinical response to treatment. Mean CD56+ lymphocyte counts (i.e., NK cells) were significantly higher than those of CD3+ cells in the 2 protocols and a subpopulation of CD56bright cells in protocol 1 was found to be preferentially expanded in vivo. Cytotoxic activity against K562 and Daudi cell lines as well as TNF-alpha and sTNF-alpha R (but not IL-6) significantly increased following treatment. Comparison of the data obtained from patients treated with IL-2 alone vs. IL-2 plus IFN-gamma did not show any significant changes except for eosinophilia (higher in protocol 1). Therefore, addition of IFN-gamma did not affect either lymphocyte distribution or non-MHC-restricted cytotoxicity in vivo. No difference in cell subpopulation or cytotoxicity was detected between responders and non-responders. Pre-treatment sTNF-alpha R concentration, in contrast to IL-6 and TNF-alpha, was significantly higher in progressive than in stable and responder groups, suggesting that this parameter may be predictive of the clinical response.
Farace
F
F
Unité d'Immunologie Cellulaire, INSERM U333, Institut Gustave Roussy, Villejuif, France.
Pallardy
M
M
Angevin
E
E
Hercend
T
T
Escudier
B
B
Triebel
F
F
D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D003602:Cytotoxicity, Immunologic; D004359:Drug Therapy, Combination; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood; D007680:Kidney Neoplasms / Q000188:drug therapy*; D007694:Killer Cells, Natural / Q000276:immunology; D009362:Neoplasm Metastasis; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007376:Interleukin-2; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma