Fabian I, Kravtsov V, Elis A, Gurevitch O, Ackerstein A, Slavin S, Nagler A
Department of Histology and Cell Biology, Sackler School of Medicine, Tel Aviv University, Israel.
Leukemia. 1994 Aug;8(8):1379-84.
We evaluated eosinophils morphology, physical properties and antileukemic activity in autologous bone marrow transplanted (ABMT) patients treated with subcutaneous recombinant interleukin 2 (rIL-2) and recombinant human interferon alpha 2a (IFN alpha) given as outpatient immunotherapy. All patients receiving rIL-2/IFN alpha therapy developed peripheral blood eosinophilia of 20-40% peaking at 2-4 weeks of therapy. While on rIL-2/IFN alpha therapy the eosinophils became hypodense and hypersegmented. The antibody dependent cell-mediated cytotoxic activity (ADCC) of the eosinophils against the human B-cell lymphoma cell line (Raji) was depressed post-ABMT. Prolonged (28 days) in vivo rIL-2/IFN alpha immunotherapy enhanced ADCC activity of the eosinophils and brought them to normal levels. Similarly, rIL-2/IFN alpha immunotherapy enhanced the depressed cytotoxic activity of neutrophils post-ABMT to normal levels. Thus, eosinophils and neutrophils from rIL-2/IFN alpha-treated ABMT recipients may be targeted toward tumor cells by antibody, and express tumoricidal activity. No effect of rIL-2/IFN alpha was observed on monocyte-dependent ADCC activity which remained normal post-ABMT. We conclude that in addition to their effect on lymphocytes, cytokine-mediated immunotherapy consisting of subcutaneous low doses of riL-2 and IFN alpha may mediate their therapeutic effects in cancer therapy by increasing the number of eosinophils and enhancing the antitumor activity of eosinophils and neutrophils, provided that tumor-specific or tumor-associated antibodies are present.
我们评估了接受皮下重组白细胞介素2(rIL-2)和重组人干扰素α2a(IFNα)门诊免疫治疗的自体骨髓移植(ABMT)患者中嗜酸性粒细胞的形态、物理特性和抗白血病活性。所有接受rIL-2/IFNα治疗的患者外周血嗜酸性粒细胞增多至20%-40%,在治疗2-4周时达到峰值。在接受rIL-2/IFNα治疗期间,嗜酸性粒细胞变得密度减低且核分叶过多。ABMT后,嗜酸性粒细胞对人B细胞淋巴瘤细胞系(Raji)的抗体依赖性细胞介导的细胞毒性活性(ADCC)降低。延长(28天)的体内rIL-2/IFNα免疫治疗增强了嗜酸性粒细胞的ADCC活性并使其恢复到正常水平。同样,rIL-2/IFNα免疫治疗将ABMT后降低的中性粒细胞细胞毒性活性提高到正常水平。因此,来自接受rIL-2/IFNα治疗的ABMT受者的嗜酸性粒细胞和中性粒细胞可能通过抗体靶向肿瘤细胞并表达杀肿瘤活性。未观察到rIL-2/IFNα对单核细胞依赖性ADCC活性有影响,该活性在ABMT后仍保持正常。我们得出结论,除了对淋巴细胞的作用外,由皮下低剂量的rIL-2和IFNα组成的细胞因子介导的免疫治疗可能通过增加嗜酸性粒细胞数量并增强嗜酸性粒细胞和中性粒细胞的抗肿瘤活性来介导其在癌症治疗中的治疗效果,前提是存在肿瘤特异性或肿瘤相关抗体。