Increased LAK and T cell activation in responding renal cell carcinoma patients after low dose cyclophosphamide, IL-2 and alpha-IFN.
Immunologic monitoring of cancer patients treated with IL-2 might help to determine functions of significance for the clinical outcome. Some immune functions in patients with advanced renal cell carcinoma were studied during treatment with low dose cyclophosphamide, alpha-interferon and IL-2. Cyclophosphamide (500 mg m-2) was given day 1, and alpha-interferon (3 x 10(6) u i.m.) and continuous infusion of IL-2 (18 x 10(6) u m-2 day-1) for days 4-9. The cycle interval was 3 weeks. Two to six cycles were given. Eleven patients entered the study. One patient achieved a partial remission, two patients had a minor response and four had a stable disease ('responding patients'). NK cell activity (K562) increased in all patients while LAK cell activity (against a renal cell carcinoma cell line, A498) was significantly augmented only in responding patients. In the responder group, there was a significant increase in CD3+/HLA-DR+ T-cells. In parallel, there was a significant decrease in CD45RA+ cells as well as in the CD4/CD8 ratio. These data might indicate an expansion of activated T cells with a reduction of cells with a suppressor phenotype in responding patients. The results corroborate the importance of activation of LAK cells and T cells during IL-2 therapy of cancer patients.
Wersäll
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Department of Oncology (Radiumhemmet), and Immunological Research Laboratory, Karolinska Hospital, Stockholm, Sweden.
Mellstedt
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H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D016898:Interferon-alpha; D007376:Interleukin-2; D003520:Cyclophosphamide