Leibovici J, Hoenig S, Pinchassov A, Barot-Ciorbaru R
Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Int J Immunopharmacol. 1994 May-Jun;16(5-6):475-80. doi: 10.1016/0192-0561(94)90039-6.
Immunomodulatory substances have been used as antineoplastic agents in experimental and human systems. Many of these agents were derived from microorganisms. Several biologically active fractions have been isolated from Nocardia. These derivatives were shown to induce interferon production, to activate natural killer cells and macrophages and to exert an antitumoral effect. We attempted to examine the mechanism of the antitumoral activity of the Nocardia water-soluble mitogen (NWSM). The tumor tested was the Lewis lung carcinoma (3LL). Regular histological examination and identification of the cellular immune reaction by monoclonal antibodies against macrophages (Mac 1 antigen), B- (IgG expressing) and T-lymphocytes (anti-Lyt-1), analysed by flow cytometry, were performed on samples of the tumor site and of the spleen. Intratumoral administration of the immunomodulators resulted in a massive accumulation of inflammatory cells around the tumor in mice treated with NWSM. The thick rim of infiltrating cells consisted of macrophages and lymphocytes, while the nontreated tumor was found to provoke only a scanty lymphocyte infiltration. Macrophages were, therefore, present at the tumor site and were directly implicated in the antitumoral effect of the Nocardia immunomodulator. T-lymphocytes were also observed at the site of the tumor. The spleen reaction consisted of marked extramedullary hematopoiesis and enlarged follicles containing prominent germinal centres (assessed also by a FACS-demonstrated increase in B-lymphocytes). In view of the inefficiency of chemotherapy in the treatment of advanced cancer, it is of major importance to explore alternative cancer treatment modalities. Immunotherapy is a particularly interesting alternative since it can potentially affect metastatic disease.
免疫调节物质已在实验系统和人体系统中用作抗肿瘤药物。这些药物许多都源自微生物。已从诺卡氏菌中分离出几种生物活性成分。这些衍生物被证明可诱导干扰素产生、激活自然杀伤细胞和巨噬细胞，并发挥抗肿瘤作用。我们试图研究诺卡氏菌水溶性促细胞分裂剂（NWSM）的抗肿瘤活性机制。所测试的肿瘤是刘易斯肺癌（3LL）。通过流式细胞术分析，对肿瘤部位和脾脏的样本进行常规组织学检查，并使用针对巨噬细胞（Mac 1抗原）、B淋巴细胞（表达IgG）和T淋巴细胞（抗Lyt-1）的单克隆抗体鉴定细胞免疫反应。在接受NWSM治疗的小鼠中，肿瘤内给予免疫调节剂导致肿瘤周围大量炎性细胞聚集。浸润细胞的厚边缘由巨噬细胞和淋巴细胞组成，而未治疗的肿瘤仅引起少量淋巴细胞浸润。因此，巨噬细胞存在于肿瘤部位，并直接参与诺卡氏菌免疫调节剂的抗肿瘤作用。在肿瘤部位也观察到了T淋巴细胞。脾脏反应包括明显的髓外造血和含有突出生发中心的增大滤泡（通过流式细胞仪检测B淋巴细胞增加也可评估）。鉴于化疗在治疗晚期癌症方面效率低下，探索替代的癌症治疗方式至关重要。免疫疗法是一种特别有吸引力的替代方法，因为它可能对转移性疾病产生影响。
