Herrlinger U, Weller M, Schabet M
Department of Neurology, University of Tuebingen, Germany.
J Neurooncol. 1998 Jun-Jul;38(2-3):233-9. doi: 10.1023/a:1005948722912.
Immunotherapeutic approaches to leptomeningeal metastasis (LM) include the intrathecal application of cytokines such as interleukin-2 (IL-2) and interferon-alpha (IFN-alpha), and lymphokine-activated killer cells (LAK cells). Results in a rodent model of leptomeningeal gliomatosis with intrathecal IL-2 application are discouraging, but some clinical improvement and clearance of neoplastic cells from CSF have been seen in patients with LM from melanoma treated with intrathecal IL-2 alone, and in patients with LM from primary brain tumors and squamous cell carcinoma of the tongue treated with intrathecal LAK cells and IL-2. The neurotoxicity of this therapy, mainly increased intracranial pressure, has been considerable but generally manageable. However, IFN-alpha caused severe neurotoxicity in form of an only partly reversible progressive vegetative state in the majority of patients. Considering the small number of patients treated with IL-2 and LAK cells, its value for the treatment of LM could only be stated by further investigation. In future, the application of recently discovered cytokines such as Fas-ligand, the continuous paracrine cytokine release by genetically modified cells, or vaccination strategies using genetically modified tumor cells might offer new immunotherapeutic approaches in LM.
针对柔脑膜转移（LM）的免疫治疗方法包括鞘内应用细胞因子，如白细胞介素-2（IL-2）和干扰素-α（IFN-α），以及淋巴因子激活的杀伤细胞（LAK细胞）。在鞘内应用IL-2的柔脑膜胶质瘤病啮齿动物模型中的结果令人沮丧，但在单独接受鞘内IL-2治疗的黑色素瘤所致LM患者，以及接受鞘内LAK细胞和IL-2治疗的原发性脑肿瘤和舌鳞状细胞癌所致LM患者中，已观察到一些临床改善以及脑脊液中肿瘤细胞的清除。该疗法的神经毒性，主要是颅内压升高，较为严重但通常可控。然而，IFN-α在大多数患者中导致了严重的神经毒性，表现为仅部分可逆的进行性植物状态。鉴于接受IL-2和LAK细胞治疗的患者数量较少，其对LM治疗的价值只能通过进一步研究来确定。未来，应用最近发现的细胞因子如Fas配体、通过基因改造细胞持续旁分泌细胞因子释放，或使用基因改造肿瘤细胞的疫苗接种策略，可能会为LM提供新的免疫治疗方法。
